PGDM1400 (mAb)

Associated long-acting platforms

Solution, Monoclonal antibodies and antibody drug conjugates

Administration route

Intravenous

Therapeutic area(s)

Use case(s)

Use of drug

Dosage

Drug information

Delivery device(s)

No delivery device

Antibody characteristics

Molecular identity

Epitope and engineering

Delivery

Scale-up prospects

Not provided

Tentative equipment list for manufacturing

Bioreactors

Manufacturing

The synthesis of PGDM1400, is typically performed using recombinant DNA technology. 1. Gene Identification and Cloning: The heavy and light chain variable regions of PGDM1400 are identified from B cells of HIV-infected individuals with broad serum neutralization. These genes are then cloned into expression vectors with appropriate constant regions (e.g., IgG1). 2. Expression: HEK293 or CHO cells 3. Purification using protein A/G affinity chromatography

Specific analytical instrument required for characterization of formulation

1. Protein A/G affinity chromatography 2. SDS-PAGE 3. HPLC 4. ELISA 5. Neutralization assay

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

Indication(s)

HIV

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

Indication(s)

HIV

Key resources

IPCAVD014/HTX1004

Identifier

NCT04983030

Link

https://clinicaltrials.gov/study/NCT04983030

Phase

Phase I/II

Status

Completed

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
2026-05-27

Estimated Primary Completion Date
2026-02-28

Estimated Completion Date
2026-04-30

Actual Primary Completion Date
2026-02-23

Actual Completion Date
2026-02-23

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

28

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

Indication(s)

HIV

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

Broadly neutralizing antibody and uses thereof

Brief description

The present invention relates to an exceptionally broad and potent neutralizing antibody which may comprise cross-clade neutralizing coverage of 83% at a median IC50 of 0.003 µg/ml, compositions containing the same and uses thereof.

Representative patent

EP2975053A1

Category

Not provided

Patent holder

Cornell University Scripps Research Institute International AIDS Vaccine Initiative Inc

Exclusivity

Not provided

Expiration date

June 10, 2035

Status

Granted in US and EPO (AT, BE, CH, DE, FR, GB, LI, NL)

Publications

Sobieszczyk, M. E., Mannheimer, S., Paez, C. A., Yu, C., Gamble, T., Theodore, D. A., Chege, W., Yacovone, M., Hanscom, B., Heptinstall, J., Seaton, K. E., Zhang, L., Miner, M. D., Eaton, A., Weiner, J. A., Mayer, K., Kalams, S., Stephenson, K., Julg, B., Caskey, M., … HVTN 130/HPTN 089 Study Team (2023). Safety, tolerability, pharmacokinetics, and immunological activity of dual-combinations and triple-combinations of anti-HIV monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered intravenously to HIV-uninfected adults: a phase 1 randomised trial. The lancet. HIV, 10(10), e653–e662. https://doi.org/10.1016/S2352-3018(23)00140-6

Link: https://doi.org/10.1016/S2352-3018(23)00140-6

Background: Preclinical and clinical studies suggest that combinations of broadly neutralising antibodies (bnAbs) targeting different HIV envelope epitopes might be required for sufficient prevention of infection. We aimed to evaluate the dual and triple anti-HIV bnAb combinations of PGDM1400 (V2 Apex), PGT121 (V3 glycan), 10-1074 (V3 glycan), and VRC07-523LS (CD4 binding site).

Methods: In this phase 1 trial (HVTN 130/HPTN 089), adults without HIV were randomly assigned (1:1:1) to three dual-bnAb treatment groups simultaneously, or the triple-bnAb group, receiving 20 mg/kg of each antibody administered intravenously at four centres in the USA. Participants received a single dose of PGT121 + VRC07-523LS (treatment one; n=6), PGDM1400 + VRC07-523LS (treatment two; n=6), or 10-1074 + VRC07-523LS (treatment three; n=6), and two doses of PGDM1400 + PGT121 + VRC07-523LS (treatment four; n=9). Primary outcomes were safety, pharmacokinetics, and neutralising activity. Safety was determined by monitoring for 60 min after infusions and throughout the study by collecting laboratory assessments (ie, blood count, chemistry, urinalysis, and HIV), and solicited and unsolicited adverse events (via case report forms and participant diaries). Serum concentrations of each bnAb were measured by binding antibody assays on days 0, 3, 6, 14, 28, 56, 112, 168, 224, 280, and 336, and by serum neutralisation titres against Env-pseudotyped viruses on days 0, 3, 28, 56, and 112. Pharmacokinetic parameters were estimated by use of two-compartment population pharmacokinetic models; combination bnAb neutralisation titres were directly measured and assessed with different interaction models. This trial is registered with ClinicalTrials.gov, NCT03928821, and has been completed.

Findings: 27 participants were enrolled from July 31, to Dec 20, 2019. The median age was 26 years (range 19-50), 16 (58%) of 27 participants were assigned female sex at birth, and 24 (89%) participants were non-Hispanic White. Infusions were safe and well tolerated. There were no statistically significant differences in pharmacokinetic patterns between the dual and triple combinations of PGT121, PGDM1400, and VRC07-523LS. The median estimated elimination half-lives of PGT121, PGDM1400, 10-1074, and VRC07-523LS were 32·2, 25·4, 27·5, and 52·9 days, respectively. Neutralisation coverage against a panel of 12 viruses was greater in the triple-bnAb versus dual-bnAb groups: area under the magnitude-breadth curve at day 28 was 3·1, 2·9, 3·0, and 3·4 for treatments one to four, respectively. The Bliss-Hill multiplicative interaction model, which assumes complementary neutralisation with no antagonism or synergism among the bnAbs, best described combination bnAb titres in the dual-bnAb and triple-bnAb groups.

Interpretation: No pharmacokinetic interactions among the bnAbs and no loss of complementary neutralisation were observed in the dual and triple combinations. This study lays the foundation for designing future combination bnAb HIV prevention efficacy trials.

Additional documents

• TAG HIV pipeline 2023

Useful links

There are no additional links