VRC07-523LS (mAb)

Drug information

Delivery device(s)

No delivery device

Scale-up prospects

Not provided

Tentative equipment list for manufacturing

Bioreactors, incubators, filtration units, lyophilizers, and formulation vessels.

Manufacturing

VRC07-5LS is a monoclonal antibody, and its production involves several key steps: VRC07-523LS is produced in a Chinese Hamster Ovary (CHO) DG44 cell line. Further information is not disclosed yet.

Specific analytical instrument required for characterization of formulation

1. Bio-Plex Instrument (Bio-Rad) 2. Beckman Biomek Automation Platform 3. Surface-Plasmon-Resonance-(SPR)-Systeme 4. Dynamic Light Scattering, 5. Differential Scanning Calorimetry 6. Circular dichroism and isothermal chemical denaturation

IAVI T003

Identifier

NCT03721510

Link

https://clinicaltrials.gov/study/NCT03721510

Phase

Phase I/II

Status

Completed

Sponsor

International AIDS Vaccine Initiative

More details

This is a Phase 1/2a open label study to evaluate the safety, tolerability, pharmacokinetics and anti-viral activity of PGT121, VRC07-523LS and PGDM1400 for HIV prevention and therapy.

Purpose

A Phase 1/2a Study of PGT121, VRC07-523LS and PGDM1400 Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2018-12-03

Anticipated Date of Last Follow-up
2022-05-06

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2021-10-25

Actual Completion Date
2022-05-02

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

1. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study. 2. In the opinion of the Principal Investigator or designee and based on Assessment of Informed Consent Understanding results, has understood the information provided and potential impact and/or risks linked to IV infusion and participation in the trial; written informed consent will be obtained from the volunteer before any study-related procedures are performed. 3. All volunteers born female engaging in sexual activity that could lead to pregnancy must commit to use an effective method of contraception from the day of the first IV infusion of investigational product until 6 months following the final investigational product administration 4. All sexually active vo

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

19

Allocation

Not provided

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

170030

Identifier

NCT03015181

Link

https://clinicaltrials.gov/study/NCT03015181

Phase

Phase I

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

Background: Human immunodeficiency virus (HIV) is a global health threat. The body uses antibodies to fight infection. VRC07-523LS is an antibody directed against HIV. It may be used to prevent mother-to-child transmission of HIV. It may also prevent sexual transmission of HIV and treat HIV-1 infected people. Objective: To test the safety, tolerability, dose, and pharmacokinetics of VRC07-523LS in healthy adults. Eligibility: Healthy people ages 18-50 Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Participants will be assigned to 1 of 7 groups: Groups 1-5 will get the drug at 1 visit and then be observed for 24 weeks. Groups 6 and 7 will get the drug at 1 visit every 12 weeks, for a total of 3 doses over 48 weeks. Participants

Purpose

VRC 605: Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered Intravenously or Subcutaneously to Healthy Adults

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2017-02-21

Anticipated Date of Last Follow-up
2020-10-21

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2018-07-10

Actual Completion Date
2018-07-10

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

* INCLUSION CRITERIA: A volunteer must meet all of the following criteria: * Able and willing to complete the informed consent process. * 18 to 50 years of age. * Based on history and examination, must be in good general health and without history of any of the conditions listed in the exclusion criteria. * Willing to have blood samples collected, stored indefinitely, and used for research purposes. * Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. * Willing to adhere to reduced risk sexual behavior during study participation. * Screening laboratory values within 84 days prior to enrollment must meet the following criteria: * White Blood Cell (WBC) 2,500-12,000/mm\^3. * WBC differential either within institutional norma

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

26

Allocation

Not provided

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

IAVI T003

Identifier

NCT03721510

Link

https://clinicaltrials.gov/study/NCT03721510

Phase

Phase I/II

Status

Completed

Sponsor

International AIDS Vaccine Initiative

More details

This is a Phase 1/2a open label study to evaluate the safety, tolerability, pharmacokinetics and anti-viral activity of PGT121, VRC07-523LS and PGDM1400 for HIV prevention and therapy.

Purpose

A Phase 1/2a Study of PGT121, VRC07-523LS and PGDM1400 Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2018-12-03

Anticipated Date of Last Follow-up
2022-05-06

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2021-10-25

Actual Completion Date
2022-05-02

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

1. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study. 2. In the opinion of the Principal Investigator or designee and based on Assessment of Informed Consent Understanding results, has understood the information provided and potential impact and/or risks linked to IV infusion and participation in the trial; written informed consent will be obtained from the volunteer before any study-related procedures are performed. 3. All volunteers born female engaging in sexual activity that could lead to pregnancy must commit to use an effective method of contraception from the day of the first IV infusion of investigational product until 6 months following the final investigational product administration 4. All sexually active vo

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

19

Allocation

Not provided

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

IMPAACT 2037

Identifier

NCT06517693

Link

https://clinicaltrials.gov/study/NCT06517693

Phase

Phase I

Status

Not yet recruiting

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of the potent, broadly neutralizing anti-HIV monoclonal antibodies (mAb) PGT121.414.LS alone and in combination with VRC07-523LS soon after birth in infants exposed to HIV-1.

Purpose

Safety and Pharmacokinetics Study of PGT121.414.LS Alone and in Combination With VRC07-523LS in Infants Exposed to HIV-1

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
2025-06-01

Actual Start Date
Not provided

Anticipated Date of Last Follow-up
2025-01-28

Estimated Primary Completion Date
2027-12-31

Estimated Completion Date
2028-06-30

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Children

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: * Birthing parent is of legal age or circumstance to provide independent informed consent and is willing and able to provide written informed consent for themselves and permission for their infant's participation in this study. * Birthing parent has confirmed HIV-1 infection based on positive test results from two samples collected from two separate blood collection tubes. * Infant was singleton or twin. * Infant's gestational age at birth was at least 36 weeks. * At birth, infant's weight was at least 2 kg. * At entry, infant is less than 72 hours of age and is anticipated to receive study product within 72 hours after birth. * At screening, infant has the following laboratory test results: * Hemoglobin, normal or grade 1 (≥13 g/dL or ≥8.05 mmol/L) * Platelets, n

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

48

Allocation

Not provided

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

HVTN 206/HPTN 114

Identifier

NCT06812494

Link

https://clinicaltrials.gov/study/NCT06812494

Phase

Phase II

Status

Recruiting

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

HVTN 206/HPTN 114 is a randomized, double blind, controlled, phase 2 clinical trial to evaluate the safety, tolerability, pharmacokinetics, and neutralization of VRC07-523LS, PGT121.414.LS, and PGDM1400LS broadly neutralizing monoclonal antibodies given intravenously in adult participants without HIV. The hypothesis of the study is that the combination of VRC07-523LS and PGT121.414.LS and PGDM1400LS antibodies when administered via the intravenous (IV) route will be safe and tolerable in adult participants without HIV. The study aims to enroll 200 participants across multiple sites with an estimated total duration of participation of eighteen (18) months.

Purpose

A Study of VRC07-523LS, PGT121.414.LS, and PGDM1400LS Broadly Neutralizing Monoclonal Antibodies Given Intravenously in Adult Participants Without HIV

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2025-03-07

Anticipated Date of Last Follow-up
2025-06-30

Estimated Primary Completion Date
2027-01-15

Estimated Completion Date
2027-09-15

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: * Participants need to be between 18 and 65 years old. * Participants must have access to a participating clinical research site and be willing to follow the study schedule. * Participants should understand the study details and be willing to give informed consent. * Participants must agree not to join any other clinical trials until they finish this study. * Participants must be willing to receive HIV test results. * Participants should be open to discussing HIV prevention. * Clinic staff should assess participants as having a low risk of getting HIV, and participants must commit to avoiding high-risk behaviors during the study. * Hemoglobin: Participant meets minimum levels depending on gender and hormone therapy status. * White Blood Cells (WBC): Should be within th

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

200

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Not provided

Key resources

18-1217

Identifier

NCT03803605

Link

https://clinicaltrials.gov/study/NCT03803605

Phase

Phase I

Status

Completed

Sponsor

University of North Carolina, Chapel Hill

More details

Adult participants (18-64 years old) with HIV-1 Infection on ART with a CD4 T cell count ≥ 350 cells/mm3 and viral suppression for ≥ 24 months will be enrolled on this study. Participants will receive two series of combination therapy consisting of one (1) intravenous (IV) dose of VRC-HIVMAB075-00-AB (VRC07-523LS) followed by 10 oral (PO) doses of Vorinostat (VOR) taken every 72 hours. Each series will last approximately 1 month and the two series will be separated by at least one month. Combination ART is maintained throughout the study. Participants will be on this study for approximately 28 weeks (or about 7 months). The purpose of this study is to: * Evaluate the safety of two series of a VRC07-523LS infusion followed by multiple oral doses of VOR * Determine if combining VRC07-523LS

Purpose

Study to Assess Safety and Activity of Combination Therapy of VRC07-523LS and Vorinostat on HIV-infected Persons

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2019-02-12

Anticipated Date of Last Follow-up
2021-11-04

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2021-01-28

Actual Completion Date
2021-01-28

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: 1. ≥ 18 years and \< 65 years of age 2. Ability and willingness of participant to give written informed consent. Note: Due to the lack of foreseeable benefit to study participants, mentally incompetent participants will not be enrolled. 3. HIV infection documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral assay. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus c

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

15

Allocation

Not provided

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

VRC07-523LS

Identifier

NCT03735849

Link

https://clinicaltrials.gov/study/NCT03735849

Phase

Phase I

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to evaluate the safety and pharmacokinetics of a human monoclonal antibody (VRC07-523LS) in the sera and mucosae of healthy, HIV-uninfected adults.

Purpose

Evaluating the Safety and Pharmacokinetics of VRC07-523LS in the Sera and Mucosae of Healthy, HIV-Uninfected Adult Participants

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2019-01-18

Anticipated Date of Last Follow-up
2025-05-23

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2020-12-21

Actual Completion Date
2020-12-21

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: General and Demographic Criteria * Age of 18 to 50 years * Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study * Ability and willingness to provide informed consent * Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly * Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit * Good general health as shown by medical history, physical exam, and screening laboratory tests HIV-Related Criteria: *

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

28

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

VRC07-523LS

Identifier

NCT03735849

Link

https://clinicaltrials.gov/study/NCT03735849

Phase

Phase I

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to evaluate the safety and pharmacokinetics of a human monoclonal antibody (VRC07-523LS) in the sera and mucosae of healthy, HIV-uninfected adults.

Purpose

Evaluating the Safety and Pharmacokinetics of VRC07-523LS in the Sera and Mucosae of Healthy, HIV-Uninfected Adult Participants

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2019-01-18

Anticipated Date of Last Follow-up
2025-05-23

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2020-12-21

Actual Completion Date
2020-12-21

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: General and Demographic Criteria * Age of 18 to 50 years * Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study * Ability and willingness to provide informed consent * Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly * Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit * Good general health as shown by medical history, physical exam, and screening laboratory tests HIV-Related Criteria: *

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

28

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

HVTN 127/HPTN 087

Identifier

NCT03387150

Link

https://clinicaltrials.gov/study/NCT03387150

Phase

Phase I

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to evaluate the safety, tolerability, and serum concentrations of a human monoclonal antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), administered in multiple doses and routes to healthy, HIV-uninfected adults.

Purpose

Evaluating the Safety and Serum Concentrations of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered in Multiple Doses and Routes to Healthy, HIV-uninfected Adults

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2018-02-28

Anticipated Date of Last Follow-up
2023-04-03

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2020-12-07

Actual Completion Date
2020-12-07

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: General and Demographic Criteria * Age of 18 to 50 years * Access to a participating clinical research site (CRS) and willingness to be followed for the planned duration of the study * Ability and willingness to provide informed consent * Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly * Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit * Good general health as shown by medical history, physical exam, and screening laboratory tests HIV-Related Criteria: * Willingness to receive HIV test re

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

124

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

AAAU5207

Identifier

NCT05890963

Link

https://clinicaltrials.gov/study/NCT05890963

Phase

Phase I

Status

Not provided

Sponsor

David Ho

More details

This is an open-label phase 1b clinical trial enrolling people living with HIV (PLWH) who are antiretroviral therapy (ART)-naïve or have not been on ART for \> 24 weeks. This study will enroll PLWH to assess the safety, tolerability, and antiviral effect of bispecific and long-acting bNAbs, alone and in combination. The study will be conducted as a single center study at National Institute for Medical Research-Mbeya Medical Research Center (NIMR-MMRC) in Mbeya, Tanzania. 20 PLWH will be sequentially enrolled into one of 5 arms, each arm comprised of 4 participants. Sequential enrollment will occur in the following order: * Arm 1 will receive standard daily oral ART. * Arm 2 will receive a single dose of 10E8.4/iMab 600mg intravenous injection (IV). * Arm 3 will receive a single dose of 1

Purpose

10E8.4/iMab Bispecific Antibody and VRC07-523LS Monoclonal Antibody in HIV-infected Adults

Interventions

Intervention 1

Intervention 2

Intervention 3

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2023-11-28

Anticipated Date of Last Follow-up
2025-04-24

Estimated Primary Completion Date
2026-04-01

Estimated Completion Date
2027-05-01

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: 1. Able to read and write in Kiswahili and/or English 2. Able and willing to provide written informed consent 3. Passes Test of Understanding (TOU) 4. Aged 18-50 years, inclusive 5. Antiretroviral Therapy (ART)-naïve or no ART for \> 24 weeks at the time of screening 6. HIV RNA 1,000-100,000 copies/mL 7. CD4 ≥ 500 cells/mm3 8. Laboratory criteria at screening within protocol-specified limits for blood, chemistry and urinalysis 9. Willing and able to participate in study visits and procedures for up to 50 weeks 10. Willing and able to begin ART as directed during the study 11. Willing and able to use barrier protection during sex with partners without HIV or partners with unknown HIV status throughout Step 1 and until viral suppression \<200 copies/mL is confirmed in St

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

20

Allocation

Not provided

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

IAVI T002

Identifier

NCT03205917

Link

https://clinicaltrials.gov/study/NCT03205917

Phase

Phase I

Status

Completed

Sponsor

International AIDS Vaccine Initiative

More details

This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGDM1400 and PGT121 and VRC07-523LS mAbs for HIV prevention and therapy.

Purpose

A Clinical Trial of PGDM1400 and PGT121 and VRC07-523LS Monoclonal Antibodies in HIV-infected and HIV-uninfected Adults

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2017-10-23

Anticipated Date of Last Follow-up
2020-09-11

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2020-04-20

Actual Completion Date
2020-04-20

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Groups 1 and 2 Inclusion Criteria: * HIV-uninfected males or females age 18-50 years old * Willing to maintain low risk behavior for HIV infection Groups 1 and 2 Exclusion Criteria: • Confirmed HIV-infection, pregnancy or lactation, significant acute or chronic disease and clinically significant laboratory abnormalities Group 3 Inclusion Criteria: * HIV-infected males or females age 18-65 years old * Not on antiretroviral therapy with HIV-1 RNA plasma level between 1,000 and 100,000 copies/ml, CD4 cell count ≥ 300 cells/uL Group 3 Exclusion Criteria: • Significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

29

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

GS-US-382-5445

Identifier

NCT05281510

Link

https://clinicaltrials.gov/study/NCT05281510

Phase

Phase II

Status

Completed

Sponsor

Gilead Sciences

More details

The goals of this clinical study are to learn more about the study drugs, VRC07-523LS, CAP256V2LS, and vesatolimod (VES) and how safe it is in women that have HIV and are on antiretroviral therapy (ART).

Purpose

Study of VRC07-523LS, CAP256V2LS, and Vesatolimod, in Early Antiretroviral-treated HIV-1 Clade C-infected Women

Interventions

Intervention 1

Intervention 2

Intervention 3

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2022-06-09

Anticipated Date of Last Follow-up
2025-01-29

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2025-01-16

Actual Completion Date
2025-01-16

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• Female

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Key Inclusion Criteria: * Age ≥ 18 years * Females recruited from the Females Rising through Education, Support, and Health (FRESH) acute human immunodeficiency virus (HIV) infection cohort. * Plasma human immunodeficiency -1 (HIV-1) ribonucleic acid (RNA) levels \< 50 copies/mL at the screening visit. * On antiretroviral (ART) regimen for ≥ 12 consecutive months prior to the screening visit. * Have all the following laboratory values at the screening visit: * Hemoglobin ≥ 10.0 g/dL * White blood cells ≥ 2500 cells/μL * Platelets ≥ 125,000/mL * Absolute neutrophil counts ≥ 1000 cells/μL * Cluster of differentiation (CD)4+ T cell count ≥ 500 cells/μL * Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin ≤ 2 × upper limit of normal (ULN) * Creatini

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

20

Allocation

Not provided

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

HVTN 130/HPTN 089

Identifier

NCT03928821

Link

https://clinicaltrials.gov/study/NCT03928821

Phase

Phase I

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of combinations of monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered via intravenous infusion in healthy, HIV-uninfected adults.

Purpose

Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Combinations of Monoclonal Antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS Administered Via Intravenous Infusion

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2019-07-17

Anticipated Date of Last Follow-up
2022-06-15

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2021-03-25

Actual Completion Date
2021-03-25

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: General and Demographic Criteria * Age of 18 to 50 years * Access to a participating clinical research site (CRS) and willingness to be followed for the planned duration of the study * Ability and willingness to provide informed consent * Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly * Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit * Good general health as shown by medical history, physical exam, and screening laboratory tests HIV-Related Criteria: * Willingness to receive HIV test re

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

27

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

160147

Identifier

NCT02840474

Link

https://clinicaltrials.gov/study/NCT02840474

Phase

Phase I

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

Background: The human body uses antibodies as one way to help fight infection. VRC01LS and VRC07-523LS are antibodies directed against the HIV virus. Researchers want to see if they are safe and well tolerated. In Part A of the study, the researchers studied VRC01LS. Part A of the study was completed in 2017. In Part B, the researchers studied VRC07-523LS. Depending on which antibody received, researchers studied the amount of VRC01LS or VRC07-523LS in the body and how it changes over time. They evaluated the effect of antibodies on CD4+ (Cluster of Differentiation 4) lymphocyte count and HIV viral load, and checked to see if people who get VRC01LS or VRC07-523LS develop an immune response to it. Objective: To see if VRC01LS and VRC07-523LS are safe and well tolerated. Eligibility: Ad

Purpose

Phase 1, Open-label, Single Dose Study to Examine Safety, Tolerability, Pharmacokinetics and Virologic Impact of VRC01LS or VRC07-523LS in HIV-infected Viremic Adults

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2017-04-24

Anticipated Date of Last Follow-up
2025-01-28

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2020-01-15

Actual Completion Date
2020-01-15

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

INCLUSION CRITERIA: A participant must meet all of the following criteria: 1. Able and willing to complete the informed consent process. 2. 18-70 years old 3. Available for clinic visits for 48 weeks after study product administration. 4. HIV-1 infected and clinically stable. \[Note: Documented HIV-1 infection by HIV enzyme immunoassay (EIA) performed by a Clinical Laboratory Improvement Amendments (CLIA) certified outside lab within 28 days of enrollment is acceptable.\] 5. At least one plasma viral load \>=500 copies/mL within 28 days of enrollment. A plasma viral load within 28 days and closest to the day of enrollment, that is detectable but not greater than 100,000 copies/mL. \[Note: outside laboratory results will be acceptable\]. 6. A CD4+ count \>=350 cells/microliter (mcL) on 2

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

16

Allocation

Not provided

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

ACHIEV

Identifier

NCT06484335

Link

https://clinicaltrials.gov/study/NCT06484335

Phase

Phase I

Status

Not yet recruiting

Sponsor

Henry M. Jackson Foundation for the Advancement of Military Medicine

More details

This is a phase I, randomized, double-blind, placebo-controlled clinical trial to investigate the safety of VRC07-523LS and PGDM1400LS in combination with ChAdOx1.tHIVconsv1, ChAdOx1.HIVconsv62 prime, MVA.tHIVconsv4 and A244d11gp120/ALFQ vaccination, and the impact on viral load setpoint during analytic treatment interruption (ATI) in people living with human immunodeficiency virus-1 (HIV-1, PLWH) who have initiated or will initiate antiretroviral therapy (ART) during acute HIV-1 infection (AHI).

Purpose

RV630 - Approach to Control HIV With Immune Enhancement and Vaccination (ACHIEV

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
2025-05-01

Actual Start Date
Not provided

Anticipated Date of Last Follow-up
2025-03-12

Estimated Primary Completion Date
2027-08-01

Estimated Completion Date
2027-08-01

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion/Exclusion Step 1 Inclusion Criteria (Groups 1 and 2 only) Participants are eligible to be included in the protocol Step 1 only if all of the following criteria are met: 1. Thai National 2. Age ≥18 and ≤60 years of age 3. Can read and write Thai 4. Able and willing to provide written informed consent 5. Confirmed HIV-1 infection (nucleic acid testing \[NAT\] and/or HIV-1 serology positive with confirmatory quantitative HIV-1 viral load) and started ART during acute infection 6. Uninterrupted treatment with ART (no interruption of ART for ≥7 consecutive days or longer) since ART initiation, for ≥ 48 weeks. 7. Currently on integrase inhibitor-based ART regimen (excluding long-acting injectable regimens) and no recent (≤8 weeks prior to screening) changes to ART regimen. a. The

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

48

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Triple-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

ACTG A5357

Identifier

NCT03739996

Link

https://clinicaltrials.gov/study/NCT03739996

Phase

Phase II

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and antiviral activity of long-acting cabotegravir (CAB LA) plus the broadly neutralizing monoclonal antibody,VRC-HIVMAB075-00-AB (VRC07-523LS), in adults living with HIV-1 with suppressed plasma viremia.

Purpose

Long-Acting Cabotegravir Plus VRC-HIVMAB075-00-AB (VRC07-523LS) for Viral Suppression in Adults Living With HIV-1

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2019-12-31

Anticipated Date of Last Follow-up
2025-05-07

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2024-04-29

Actual Completion Date
2024-04-29

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Step 1 Inclusion Criteria * HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load. * NOTE: The term "licensed" refers to a US Food and Drug Administration (FDA)-approved kit, which is required for all IND studies. * World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

75

Allocation

Not provided

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

ACTG A5357

Identifier

NCT03739996

Link

https://clinicaltrials.gov/study/NCT03739996

Phase

Phase II

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and antiviral activity of long-acting cabotegravir (CAB LA) plus the broadly neutralizing monoclonal antibody,VRC-HIVMAB075-00-AB (VRC07-523LS), in adults living with HIV-1 with suppressed plasma viremia.

Purpose

Long-Acting Cabotegravir Plus VRC-HIVMAB075-00-AB (VRC07-523LS) for Viral Suppression in Adults Living With HIV-1

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2019-12-31

Anticipated Date of Last Follow-up
2025-05-07

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2024-04-29

Actual Completion Date
2024-04-29

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Step 1 Inclusion Criteria * HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load. * NOTE: The term "licensed" refers to a US Food and Drug Administration (FDA)-approved kit, which is required for all IND studies. * World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

75

Allocation

Not provided

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

IPCAVD014/HTX1004

Identifier

NCT04983030

Link

https://clinicaltrials.gov/study/NCT04983030

Phase

Phase I/II

Status

Not provided

Sponsor

Boris Juelg, MD PhD

More details

A multicenter, randomized, parallel-group, placebo-controlled, double-blind, Phase 1/2a clinical study to investigate the safety, tolerability, immunogenicity and exploratory efficacy of a vaccine regimen consisting of an Ad26.Mos4.HIV prime and a boost with Modified Vaccinia Ankara (MVA)-BN-HIV in combination with broadly neutralizing antibodies (bNAb) PGT121, PGDM1400, and VRC07-523LS in human immunodeficiency virus type 1 (HIV-1)-infected study participants on suppressive anti-retroviral therapy (ART).

Purpose

Safety, Immunogenicity, Efficacy of Ad26.Mos4.HIV, MVA-BN-HIV and PGT121, PGDM1400, and VRC07-523LS in HIV-1-Infected Adults

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2022-04-01

Anticipated Date of Last Follow-up
2025-02-03

Estimated Primary Completion Date
2026-02-28

Estimated Completion Date
2026-04-30

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: 1. Each potential study participant must pass the Test of Understanding (TOU), indicating that he or she understands the purpose of, and procedures required for the study, after reading the informed consent and after the investigator or designee has provided detailed information on the study and has answered the potential study participant's questions. Each study participant must subsequently sign the ICF, indicating that he or she is willing to participate in the study. 2. Each study participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol. 3. Study participants are ≥18 to ≤70 years old on the day of signing the ICF. 4. Each study participant must have documented HIV-1 infection. 5. Must be on suppressive ART for a

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

36

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Not provided

Use case

Treatment

Key resources

HVTN 140/HPTN 101

Identifier

NCT05184452

Link

https://clinicaltrials.gov/study/NCT05184452

Phase

Phase I

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

Part A: The purpose of this part of the study is to understand how the body's immune system responds to a new lab-made antibody against HIV. The study is looking to see if the way the antibody is given affects the immune response. The study will also look at whether the antibody is safe to give to people and does not make them too uncomfortable. Part B: The purpose of this part of the study is to understand how the body's immune system responds to lab-made antibodies against HIV when they are given in combination at different doses. The study also wants to see if the way the antibodies are given affects the immune response.

Purpose

A Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of PGDM1400LS Alone and in Combination With VRC07-523LS and PGT121.414.LS in Healthy, HIV-uninfected Adult Participants

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2021-11-15

Anticipated Date of Last Follow-up
2025-01-16

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2023-07-19

Actual Completion Date
2023-07-19

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: 1. Age of 18 through 50 years 2. Access to a participating CRS and willingness to be followed for the planned duration of the study 3. Ability and willingness to provide informed consent 4. Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly 5. Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit. 6. Good general health as shown by medical history, physical exam, and screening laboratory tests 7. Willingness to receive HIV test results 8. Willingness to discuss HIV infection risks and amenable to HI

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

95

Allocation

Randomized

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

RV582

Identifier

NCT05769569

Link

https://clinicaltrials.gov/study/NCT05769569

Phase

Phase I

Status

Withdrawn

Sponsor

Henry M. Jackson Foundation for the Advancement of Military Medicine

More details

This is a phase I, randomized, open-label trial to investigate the safety of VRC07-523LS, PGDM1400LS and N-803 in combination with Ad26.Mos4.HIV, MVA-Bavarian Nordic (BN)-HIV and A244d11gp120/ALFQ vaccination, and the impact on time to sustained viral rebound of ≥1000 copies/mL for 4 consecutive weeks during analytic treatment interruption (ATI) in people living with human immunodeficiency virus-1 (HIV-1, PLWH) who initiated antiretroviral therapy (ART) during acute HIV-1 infection (AHI).

Purpose

Safety and Efficacy of Neutralizing Antibodies and Vaccination for Induction of HIV Remission

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
2023-09-01

Actual Start Date
Not provided

Anticipated Date of Last Follow-up
2024-05-02

Estimated Primary Completion Date
2025-07-01

Estimated Completion Date
2025-07-01

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Step 1 Inclusion Criteria Participants are eligible to be included in the protocol Step 1 only if all of the following criteria are met: 1. Thai National 2. Age ≥18 and ≤50 years of age 3. Can read and write Thai or English 4. Able and willing to provide written informed consent 5. Participant of the RV254 study 6. Confirmed HIV-1 infection (nucleic acid testing \[NAT\] and/or HIV serology positive with confirmatory quantitative HIV viral load) and started ART during acute infection (Fiebig stage I-V) 7. Uninterrupted treatment with ART (no interruption of ART for ≥7 consecutive days or longer) since ART initiation, for ≥ 48 weeks. 8. Currently on integrase inhibitor-based ART regimen (excluding long-acting injectable regimens) and no recent (≤8 weeks prior to screening) changes to ART r

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

Not provided

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

HVTN 136/HPTN 092

Identifier

NCT04212091

Link

https://clinicaltrials.gov/study/NCT04212091

Phase

Phase I

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of the monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS via intravenous or subcutaneous infusions in healthy, HIV-uninfected adult participants.

Purpose

Evaluating the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of the Monoclonal Antibody PGT121.414.LS Administered Alone and in Combination With VRC07-523LS Via Intravenous or Subcuta

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2020-11-10

Anticipated Date of Last Follow-up
2024-12-10

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2023-01-18

Actual Completion Date
2023-01-18

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: General and Demographic Criteria * Age of 18 to 50 years * Access to a participating Clinical Research Site (CRS) and willingness to be followed for the planned duration of the study * Ability and willingness to provide informed consent * Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly * Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit * Good general health as shown by medical history, physical exam, and screening laboratory tests HIV-Related Criteria: * Willingness to receive HIV test re

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

33

Allocation

Randomized

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

180113

Identifier

NCT03565315

Link

https://clinicaltrials.gov/study/NCT03565315

Phase

Phase I

Status

Terminated

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

Background: Human immunodeficiency virus (HIV) infection is a serious disease. There is no cure or vaccine to prevent infection. Using antibodies might be a good way to treat or prevent HIV. Antibodies are naturally made by the body to fight germs. Researchers want to test if two antibodies made artificially in a lab can help to prevent HIV infection. The antibodies are 10E8VLS and VRC07-523LS. Objective: To see if 10E8VLS and VRC07-523LS are safe and well-tolerated and how long they stay in the blood. Eligibility: Healthy adults ages 18-60 Design: Volunteers were screened in another protocol. Participants were enrolled in 1 of 4 groups: Group 1 participants were enrolled to receive 1 dose of 10E8VLS. Group 2 participants were enrolled to receive 3 doses of 10E8VLS. Group 3 part

Purpose

Phase I Study to Evaluate a Human Monoclonal Antibody (MAb) 10E8VLS Administered Alone or Concurrently With MAb VRC07-523LS Via Subcutaneous Injection in Healthy Adults

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2018-07-10

Anticipated Date of Last Follow-up
2020-12-08

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2019-03-04

Actual Completion Date
2019-03-04

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

* INCLUSION CRITERIA: 1. Willing and able to complete the informed consent process. 2. 18 to 60 years of age. 3. Based on history and examination, in good general health and without history of any of the conditions listed in the exclusion criteria. 4. Willing to have blood samples collected, stored indefinitely, and used for research purposes. 5. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. 6. Screening laboratory criteria within 84 days prior to enrollment must meet the following criteria: * White blood cell count (WBC): 2,500-12,000/mm\^3. * WBC differential: Within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval. * Platelets: 125,000 - 400,000/mm\^3. * Hemogl

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

9

Allocation

Not provided

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

ACTG A5386

Identifier

NCT04340596

Link

https://clinicaltrials.gov/study/NCT04340596

Phase

Phase I

Status

Not provided

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to evaluate the safety, tolerability, and efficacy of N-803, an IL-15 superagonist, with or without combination broadly neutralizing antibodies (bNAbs), to induce HIV-1 control during analytic treatment interruption (ATI).

Purpose

Safety, Tolerability, and Efficacy of IL-15 Superagonist (N-803) With and Without Combination Broadly Neutralizing Antibodies to Induce HIV-1 Control During Analytic Treatment Interruption

Interventions

Intervention 1

Intervention 2

Intervention 3

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2021-05-21

Anticipated Date of Last Follow-up
2025-03-24

Estimated Primary Completion Date
2026-06-30

Estimated Completion Date
2026-12-30

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria * HIV-1 infection * On ART for at least 96 weeks prior to randomization * On ART regimen containing an integrase inhibitor and two nucleoside reverse transcriptase inhibitors (NRTIs) or dolutegravir/lamivudine for at least 6 weeks prior to randomization. * CD4 cell count \>450 cells/mm\^3 within 90 days prior to randomization * CD4 cell count nadir ≥200 cells/mm\^3. * Plasma HIV-1 RNA levels of \<50 copies/mL for at least 96 weeks prior to randomization * Select laboratory results within 90 days of randomization * IC90 to 10-1074 of ≤1.5 mcg/mL, 10-1074 maximum percent inhibition (MPI) ≥98%, and IC80 to VRC07-523LS of ≤1 mcg/mL on the Monogram PhenoSense assay. * QTcF interval ≤440 msec within 90 days prior to randomization. * For cisgender women and transgender men of

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

118

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

IMPAACT P1112

Identifier

NCT02256631

Link

https://clinicaltrials.gov/study/NCT02256631

Phase

Phase I

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study was to assess the safety and pharmacokinetics (PK) of three monoclonal antibodies, VRC01, VRC01LS, and VRC07-523LS, in HIV-exposed infants who are at increased risk of mother-to-child HIV transmission.

Purpose

Evaluating the Safety and Pharmacokinetics of VRC01, VRC01LS, and VRC07-523LS, Potent Anti-HIV Neutralizing Monoclonal Antibodies, in HIV-1-Exposed Infants

Interventions

Not provided

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2015-06-30

Anticipated Date of Last Follow-up
2023-01-12

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2020-06-17

Actual Completion Date
2021-12-16

Studied populations

Age Cohort

• Children

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Maternal Inclusion Criteria: * HIV infection * Greater than or equal to 18 years of age * Able and willing to provide signed informed consent for herself and her infant Maternal Exclusion Criteria: * Prior participation in any HIV-1 vaccine trial * Receipt of any other active or passive HIV immunotherapy or investigational product during this pregnancy. (Note that administration of Food and Drug Administration \[FDA\]-approved antiretroviral (ARV) drugs when used to treat disease or prevent mother-to-child transmission were not considered investigational.) * Documented or suspected serious medical illness or immediate life-threatening condition (other than HIV infection) in the mother that may have interfered with the ability to complete study requirements, as judged by the examining cl

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

83

Allocation

Not provided

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

IMPAACT 2042

Identifier

NCT06508749

Link

https://clinicaltrials.gov/study/NCT06508749

Phase

Phase I/II

Status

Recruiting

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study is to advance pediatric HIV treatment and cure research by evaluating the impact of a combination of three anti-HIV-1 broadly neutralizing antibodies (bNAbs) or analytic treatment interruption (ATI) on viral reservoir, immune function, and maintenance of HIV suppression in early-treated children.

Purpose

The Tatelo Plus Study

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2024-11-11

Anticipated Date of Last Follow-up
2025-06-09

Estimated Primary Completion Date
2027-11-05

Estimated Completion Date
2028-04-21

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Children
• Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria, Step 1 * Previously enrolled in the EIT/Tatelo, or Moso Cohort Study * Receiving prescribed ART for at least 24 weeks prior to study entry as determined by the site investigator based on participant/parent/guardian report and available medical records * 24 weeks to 12 years of age at enrollment, inclusive * If entering Step 1a: HIV-1 RNA \<40 copies/mL for at least 24 weeks prior to entry, including documented suppression to \<40 copies/mL within 30 days of Step 1 entry * If entering Step 1b: HIV-1 RNA \<200 copies/mL for at least 24 weeks prior to entry, including documented suppression to \<40 copies/mL within 30 days of Step 1 entry. * Normal temperature (\<37.4°C axillary, or \<38°C non-axillary) and no signs or symptoms of acute illness at entry as determined by t

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

41

Allocation

Not provided

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

STUDY00007810

Identifier

NCT04144335

Link

https://clinicaltrials.gov/study/NCT04144335

Phase

Phase I/II

Status

Withdrawn

Sponsor

University of Minnesota

More details

To assess the safety of combination immune therapy in HIV-infected participants whose HIV is controlled with ART, by determining the incidence and severity of adverse events.

Purpose

N-803 Combined With the Broadly Neutralizing Antibodies Plus or Minus haNK Cells for HIV

Interventions

Intervention 1

Intervention 2

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
2020-01-01

Actual Start Date
Not provided

Anticipated Date of Last Follow-up
2020-10-21

Estimated Primary Completion Date
2020-12-31

Estimated Completion Date
2020-12-31

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: * HIV-1 infection * On continuous antiretroviral therapy for \> 12 months without any interruptions of greater than 14 consecutive days in the last 12 months * Screening plasma HIV RNA levels \< 20 copies/mL on all available determinations in past 12 months (isolated single values ≥ 20 but \< 200 copies/mL will be allowed if they were preceded and followed by viral load determinations \< 20 copies/mL) * Screening CD4+ T-cell count ≥ 400 cells/mm3 Exclusion Criteria: * Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study * Active or recent malignancy requiring systemic chemotherapy or surgery in the preceding 36 months or for whom such therapies are expected in the subsequent 12 months; minor surgical removal of localized s

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

Not provided

Allocation

Randomized

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

IMPAACT P1115

Identifier

NCT02140255

Link

https://clinicaltrials.gov/study/NCT02140255

Phase

Phase I/II

Status

Recruiting

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The study will explore the effects of early intensive antiretroviral therapy (ART) with or without a broadly neutralizing antibody (bNAb) on achieving HIV remission (HIV RNA below the limit of detection of the assay) among infants living with HIV.

Purpose

Very Early Intensive Treatment of Infants Living With HIV to Achieve HIV Remission

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2015-01-23

Anticipated Date of Last Follow-up
2025-04-03

Estimated Primary Completion Date
2028-01-31

Estimated Completion Date
2031-12-31

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Children

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Maternal Inclusion Criteria 1. Presumed or confirmed maternal HIV infection: * Mothers will be eligible to enroll with EITHER: * Presumed HIV infection defined as at least one positive rapid HIV antibody-based test result from a sample collected in the peripartum period. Presumed infection must be confirmed within 10 business days of enrollment OR * Confirmed HIV infection defined as positive results from two samples collected at different timepoints 2. Willing and able to provide written informed consent for participation of herself and her infant. The mother must be of legal age or circumstance to provide independent informed consent as determined by site standard operating procedures (SOPs) and consistent with IRB/EC policies and procedures. Otherwise, informed consent m

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

1120

Allocation

Not provided

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

A5388

Identifier

NCT05719441

Link

https://clinicaltrials.gov/study/NCT05719441

Phase

Phase II

Status

Suspended

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

A5388 is a phase II, two-arm, randomized, double-blind, placebo-controlled study that will enroll 48 antiretroviral therapy (ART)-naïve adults with acute HIV infection (AHI) in order to determine whether: * Administration of combination HIV-specific broadly neutralizing antibody (bNAb) therapy in addition to ART during acute HIV infection (AHI) will be safe. * Participants who receive combination bNAb therapy in addition to ART during AHI will be more likely to demonstrate a delay in time to HIV-1 RNA ≥1,000 copies/mL for 4 consecutive weeks compared to participants who receive placebo plus ART. * Participants who receive combination bNAb therapy in addition to ART during AHI will demonstrate lower viral reservoirs and enhanced HIV-specific immunity compared to participants who receive pl

Purpose

A Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2024-08-19

Anticipated Date of Last Follow-up
2025-04-17

Estimated Primary Completion Date
2028-04-06

Estimated Completion Date
2028-09-06

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Inclusion Criteria: Step 1: 1. Appropriate documentation from medical records of diagnosis of AHI prior to enrollment that includes one of the following: 1. A detectable HIV-1 RNA within 28 days prior to study entry AND a non-reactive HIV-1 antibody within 7 days prior to entry; OR 2. A detectable HIV-1 RNA or a reactive HIV-1 antibody within 28 days prior to study entry AND a negative/indeterminate Western Blot (WB) or negative/indeterminate Geenius HIV-1/HIV-2 Supplemental Assay within 7 days prior to entry; OR 3. A documented non-reactive HIV-1 antibody or negative HIV-1 RNA within 90 days prior to study entry AND a documented reactive HIV-1 antibody or positive WB that is negative for p31 band or a positive Geenius HIV-1/HIV-2 Supplemental Assay that is negative for p31 ban

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

48

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Double-blind masking

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

18-26957

Identifier

NCT04357821

Link

https://clinicaltrials.gov/study/NCT04357821

Phase

Phase I/II

Status

Not provided

Sponsor

University of California, San Francisco

More details

Combination approaches will almost certainly be required to generate durable control of HIV in the absence of antiretroviral therapy (a "remission"). In this study, 20 individuals will receive a combination regimen administered during ART and then undergo an analytic treatment interruption (ATI).

Purpose

Combinatorial Therapy to Induce an HIV Remission

Interventions

Intervention 1

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2020-08-01

Anticipated Date of Last Follow-up
2025-05-19

Estimated Primary Completion Date
2025-12-01

Estimated Completion Date
2025-12-01

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Key Inclusion Criteria 1. Willing and able to provide written informed consent. 2. Age ≤67 years at the time of enrollment for those who started treatment during early infection and \<65 years for those who started treatment during chronic infection. 3. Documented HIV-1 infection. 4. On continuous antiretroviral therapy for at least 12 months without any interruptions of greater than 14 consecutive days within the last 1 year, and on a stable regimen that does not include an non-nucleoside reverse transcriptase inhibitor (NNRTI) for at least 4 weeks, without plans to modify ART during the study period. 5. Screening plasma HIV RNA levels below the level of quantification on all available determinations in past 24 months. 6. Screening CD4+ T-cell count ≥ 500 cells/mm3. Key Exclusion Criter

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

11

Allocation

Not provided

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

ACTG A5357

Identifier

NCT03739996

Link

https://clinicaltrials.gov/study/NCT03739996

Phase

Phase II

Status

Completed

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

The purpose of this study was to assess the safety, tolerability, antiviral activity, and pharmacokinetics of long-acting cabotegravir (CAB LA) plus the broadly neutralizing monoclonal antibody VRC-HIVMAB075-00-AB (VRC07-523LS), in adults living with HIV-1 with suppressed plasma viremia.

Purpose

Long-Acting Cabotegravir Plus VRC-HIVMAB075-00-AB (VRC07-523LS) for Viral Suppression in Adults Living With HIV-1

Interventions

Intervention 1

Intervention 2

Intervention 3

Intervention 4

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2019-12-31

Anticipated Date of Last Follow-up
2025-05-07

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2024-04-29

Actual Completion Date
2024-04-29

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
Unspecified

Accepts lactating individuals
Unspecified

Accepts healthy individuals
No

Comments about the studied populations

Step 1 Inclusion Criteria: * Individual with HIV-1 * On a three-drug ART regimen for at least 8 weeks that includes a boosted protease inhibitor (PI), a nonnuceloside reverse transcriptase inhibitor (NNRTI), or an integrase inhibitor (INSTI) plus two nuclesodie reverse transcriptase inhibitors (NRTI) with no history of switch due to virologic failure. * CD4+ cell count greater than or equal to 350 cells/mm\^3 * Virally suppressed (\< 50 copies/mL) within 2 years prior to study entry * Susceptibility to VRC07-523LS based on IC50 less than or equal to 0.25 ug/mL and a Maximum Percent Inhibition \> 98% using the Monogram PhenoSense Assay * Certain laboratory values obtained within 60 days prior to study entry and in an acceptable range * For participants of child-bearing potential: * A ne

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

75

Allocation

Not provided

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

Not provided

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key resources

Proprietary excipients used

No proprietary excipient used

Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration

No novel excipient or existing excipient used

Residual solvents used

No residual solvent used

Description

VRC07-523LS antibody

Brief description

Antibodies and antigen binding fragments that specifically bind to HIV-1 Env and neutralize HIV-1 are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV-1 using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV-1 infection is disclosed.

Representative patent

WO2019165122

Category

Compound

Patent holder

The United States of America

Exclusivity

Not provided

Expiration date

February 21, 2039

Status

Granted: US Pending: AU, CA, CN, EP, IN

Publications

Mahomed, S., Garrett, N., Capparelli, E. V., Osman, F., Harkoo, I., Yende-Zuma, N., Gengiah, T. N., Archary, D., Samsunder, N., Baxter, C., Mkhize, N. N., Modise, T., Carlton, K., McDermott, A., Moore, P. L., Karim, Q. A., Barouch, D. H., Fast, P. E., Mascola, J. R., Ledgerwood, J. E., … Abdool Karim, S. S. (2022). Safety and Pharmacokinetics of Monoclonal Antibodies VRC07-523LS and PGT121 Administered Subcutaneously for Human Immunodeficiency Virus Prevention. The Journal of infectious diseases, 226(3), 510–520. https://doi.org/10.1093/infdis/jiac041

Abstract

Background: Effective, long-acting prevention approaches are needed to reduce human immunodeficiency virus (HIV) incidence. We evaluated the safety and pharmacokinetics of VRC07-523LS and PGT121 administered subcutaneously alone and in combination as passive immunization for young women in South Africa.

Methods: CAPRISA 012A was a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 trial. We enrolled 45 HIV-negative women into 9 groups and assessed safety, tolerability, pharmacokinetics, neutralization activity, and antidrug antibody levels. Pharmacokinetic modeling was conducted to predict steady-state concentrations for 12- and 24-weekly dosing intervals.

Results: VRC07-523LS and PGT121, administered subcutaneously, were safe and well tolerated. Most common reactogenicity events were injection site tenderness and headaches. Nine product-related adverse events were mild and transient. Median VRC07-523LS concentrations after 20 mg/kg doses were 9.65 μg/mL and 3.86 μg/mL at 16 and 24 weeks. The median week 8 concentration after the 10 mg/kg PGT121 dose was 8.26 μg/mL. Modeling of PGT121 at 20 mg/kg showed median concentrations of 1.37 μg/mL and 0.22 μg/mL at 16 and 24 weeks. Half-lives of VRC07-523LS and PGT121 were 29 and 20 days. Both antibodies retained neutralizing activity postadministration and no antidrug antibodies were detected.

Conclusions: Subcutaneous administration of VRC07-523LS in combination with optimized versions of PGT121 or other antibodies should be further assessed for HIV prevention.

Gaudinski, M. R., Houser, K. V., Doria-Rose, N. A., Chen, G. L., Rothwell, R. S. S., Berkowitz, N., Costner, P., Holman, L. A., Gordon, I. J., Hendel, C. S., Kaltovich, F., Conan-Cibotti, M., Gomez Lorenzo, M., Carter, C., Sitar, S., Carlton, K., Gall, J., Laurencot, C., Lin, B. C., Bailer, R. T., … VRC 605 study team (2019). Safety and pharmacokinetics of broadly neutralising human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical trial. The lancet. HIV, 6(10), e667–e679. https://doi.org/10.1016/S2352-3018(19)30181-X

Abstract

Background:

Human monoclonal antibodies that potently and broadly neutralize HIV-1 (bnMAbs) are under development to prevent and treat HIV-1 infection. We performed a phase 1 clinical trial to determine the safety, tolerability, and pharmacokinetic profile of the bnMAb VRC07–523LS, an engineered variant of VRC01 that targets the CD4 binding-site of the HIV-1 Env protein.

Methods:

This phase 1, open-label, dose-escalation clinical trial was done at the National Institutes of Health Clinical Center in Bethesda, MD, USA. Individuals were recruited from the greater Washington, DC, area by IRB-approved written and electronic media. We enrolled healthy, HIV-1-negative adults aged 18–50 years. Inclusion criteria were good general health, measured through clinical laboratory tests, medical history, and physical examination. Participants self-selected into one of seven open groups during enrollment without randomization. Four groups received a single intravenous dose of 1, 5, 20, or 40 mg/kg of VRC07–523LS, and one group received a single 5 mg/kg subcutaneous dose. Two groups received three doses of either 20 mg/kg intravenous VRC07–523LS, or 5 mg/kg subcutaneous VRC07–523LS at 12-week intervals. The primary outcome was the safety and tolerability of VRC07–523LS, assessed by dose, route, and number of administrations. This study is registered with ClinicalTrials.gov, NCT03015181.

Findings:

Between Feb 21, 2017, and September 13, 2017, we enrolled 26 participants, including 11 (42%) men and 15 (58%) women. Two (8%) participants withdrew from the study early: one participant in group 1 enrolled in the study but never received VRC07–523LS, and one participant in group 6 chose to withdraw after a single administration. One (4%) participant in group 7 received only one of the three scheduled administrations. 17 participants received intravenous administrations and 8 participants received subcutaneous administrations. Local and systemic reactogenicity were mild to moderate when reported. The most commonly reported symptoms following IV administration included malaise or myalgia in three participants (18%) and headache or chills in two participants (12%). Following SC administration, the most commonly reported symptoms included pain and tenderness in four participants (50%) and malaise or headache in three participants (38%). No serious adverse events or dose-limiting toxicities occurred.

Interpretations:

We found VRC07–523LS to be safe and well tolerated. These qualities make VRC07–523LS a strong and practical candidate for inclusion in HIV-1 prevention and therapeutic strategies. The results from this trial also indicate that an HIV-1 bnMAb engineered to improve pharmacokinetic properties and neutralization activity can be safe for clinical use.

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