PGDM1400LS (mAb)

Associated long-acting platforms

Monoclonal antibodies and antibody drug conjugates

Administration route

Subcutaneous, 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

Not provided

Manufacturing

Not provided

Specific analytical instrument required for characterization of formulation

Not provided

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

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

Study type

Interventional (clinical trial)

Enrollment

95

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

Prevention

Indication(s)

HIV

Key resources

HVTN 206/HPTN 114

Identifier

NCT06812494

Link

https://clinicaltrials.gov/study/NCT06812494

Phase

Phase II

Status

Active, not 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

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2025-03-07

Anticipated Date of Last Follow-up
2026-08-19

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

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

Prevention, PrEP

Indication(s)

HIV

Key resources

HVTN 141/HPTN 105

Identifier

NCT07390955

Link

https://clinicaltrials.gov/study/NCT07390955

Phase

Phase I

Status

Recruiting

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

This study is testing a lab-made antibody called ePGT121v1-LS that targets a specific part of HIV. Researchers will give it by vein (IV) and under the skin (SC), both on its own and together with two other antibodies, VRC07-523LS and PGDM1400LS, which target different parts of the virus. They will assess safety and side effects, determine the right dose, study how the body processes the drug (pharmacokinetics or PK), and measure how well it neutralizes HIV in the blood (serum neutralizing activity). The expectation is that ePGT121v1-LS, whether given alone or with PGDM1400LS and VRC07-523LS, by IV or SC, will be safe in generally healthy adults and that the antibodies will not interfere with each other when used together.

Purpose

A Study of Safety and Drug Levels of ePGT121v1-LS, PGDM1400LS, and VRC07-523LS in Adult Participants Without HIV-1

Interventions

Intervention 1

Intervention 2

Intervention 5

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2026-03-19

Anticipated Date of Last Follow-up
2026-08-31

Estimated Primary Completion Date
2027-08-30

Estimated Completion Date
2027-08-30

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Inclusion Criteria: 1. Age 18 to 55 years. 2. Can visit a participating clinic and is willing to stay in the study for its full duration. 3. Understands the study and is able and willing to give informed consent. 4. Agrees not to join another experimental study until the final required clinic visit. 5. In good overall health based on medical history, physical exam, and screening lab tests. 6. Willing to receive HIV test results. 7. Willing to discuss personal risk of getting HIV and to have HIV prevention counseling. 8. Judged by clinic staff to have a low risk of getting HIV and agrees to avoid higher risk behaviors through the last clinic visit. 9. Hemoglobin levels: * Women: at least 11.0 g/dL * Men: at least 13.0 g/dL 10. White blood cell count between 2,500 and 12,000 cells/mm

Health status

Study type

Interventional (clinical trial)

Enrollment

83

Allocation

Non-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

Prevention, PrEP, Treatment

Indication(s)

HIV

Key resources

Tatelo plus - IMPAACT 2042

Identifier

NCT06508749

Link

https://clinicaltrials.gov/study/NCT06508749

Phase

Phase I/II

Status

Active, not 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
2026-09-09

Estimated Primary Completion Date
2027-09-03

Estimated Completion Date
2028-02-18

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Neonates (0 to 28 days)
• Infants (0 to 12 months)
• 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

Study type

Interventional (clinical trial)

Enrollment

41

Allocation

Non-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

Indication(s)

HIV

Key resources

ACHIEV

Identifier

NCT06484335

Link

https://clinicaltrials.gov/study/NCT06484335

Phase

Phase I

Status

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). this regimen pairs PGDM1400LS with VRC07-523LS only, without a V3-glycan antibody.

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
2025-03-27

Anticipated Date of Last Follow-up
2026-09-03

Estimated Primary Completion Date
2029-07-17

Estimated Completion Date
2029-07-17

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

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, ART-free remission strategy

Indication(s)

HIV

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
No

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

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, ART-free remission strategy

Indication(s)

HIV

Key resources

Proprietary excipients used

Not provided

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

Not provided

Residual solvents used

Not provided

There are either no relevant patents or these were not yet submitted to LAPaL

Publications

Proof-of-Concept Development and Preclinical Evaluation of a Microarray Patch Platform for Codelivery of Multiple Broadly Neutralizing Antibodies for HIV Prevention.

Peet, M. M. — Molecular Pharmaceutics — 2026-07-14

Link: https://pubs.acs.org/mpohbp/article/23/8/4048/5210144/Proof-of-Concept-Development-and-Preclinical

Broadly neutralizing antibodies (bnAbs) are advancing as a preventative or treatment option for HIV infection, but currently must be administered parenterally, typically as a large injection or infusion, an invasive method of delivery, especially for the pediatric population. Here, we present proof-of-concept data on a minimally invasive microneedle (MN) patch platform codelivering three bnAbs, PGT121, VRC07-523LS, and PGDM1400LS, from separate MN patch units or pixels. Each 1 cm2 patch pixel, fabricated via solvent casting, contained ∼2 mg of one bnAb. In ex vivo porcine skin tests, the MNs effectively penetrated the skin. When tested in vitro in PBS buffer, MNs quickly dissolved, fully releasing bnAbs within 10 min. VRC07-523LS and PGT121 functionality was maintained during patch manufacturing, as confirmed by an in vitro HIV-1 neutralization assay, while PGDM1400LS lost some potency. In a rat model, coadministration of 1 cm2 patch units for each bnAb resulted in systemic exposure by the first collection time point of 3 h, reaching maximal concentrations by day 3 of up to 68 μg/mL. These preliminary findings suggest that the MN patch platform may serve as a promising alternative to injectable bnAb formulations for HIV prevention and treatment, particularly in neonates and infants, although further investigation is required to establish its clinical utility. Additionally, the solid-state MN formulation of bnAbs may eliminate the need for cold-chain storage or distribution, making the patch particularly suitable for use in resource-limited settings.

Safety, pharmacokinetics, and neutralisation activity of PGDM1400LS, VRC07-523LS, and PGT121.414.LS infused intravenously or subcutaneously (HVTN 140/HPTN 101 part B): a phase 1, randomised trial.

Mahomed, S. et al. for HVTN 140/HPTN 101 Study Team — The Lancet HIV — 2026-07-13

Link: https://pubmed.ncbi.nlm.nih.gov/42114530/

Background: Passive immunisation with a combination of broadly neutralising monoclonal antibodies (mAbs) presents a potential HIV-1 prevention modality. This study (HVTN 140/HPTN 101) sought to evaluate PGDM1400LS (targeting V3-glycan) administered alone (part A, previously reported), and in combination (part B) with VRC07-523LS (targeting CD4 binding site) and PGT121.414.LS (targeting V2-apex) in healthy adults without HIV-1.

Methods: The study was a phase 1, multicentre, randomised, open-label trial done across the USA (five sites), Kenya (one site), South Africa (four sites), and Zimbabwe (three sites). Part B participants were randomly assigned to five groups (n=16 each), all receiving the three mAbs at months 0 and 4: infusion group T6 (20 mg/kg each mAb intravenously), T7 (20 mg/kg each mAb subcutaneously), T8 (1·4 g each mAb intravenously), T9 (1·4 g each mAb subcutaneously), and T10 (40 mg/kg each mAb intravenously). Primary endpoints were safety and tolerability throughout the study, and pharmacokinetics and neutralising activity on days 0, 3, 6, 28, 56, 112, 168, 224, and 280. Serum mAb concentrations over time were assessed via a validated anti-idiotype binding assay and analysed with two-compartment population pharmacokinetics models. Serum neutralisation titres were assessed by a validated TZM-bl assay. The study is registered at ClinicalTrials.gov (NCT05184452) and is complete.

Findings: For the 80 part B participants enrolled from March 21 to Oct 5, 2022, the median age was 27·0 years, with 47·5% females. Most participants had mild-to-moderate solicited local and systemic symptoms. No serious adverse events were reported. On the basis of pharmacokinetics data from part A and part B combined, the estimated elimination half-life of PGDM1400LS was 53 days (51·4-55·3). Subcutaneous administration of PGDM1400LS exhibited bioavailability of 73·0% (67·5-78·5%) relative to intravenous administration of the same dose. PGT121.414.LS had an estimated elimination half-life of 65 days (61·8-68·1) with subcutaneous bioavailability of 77·7% (71·2-84·1), and VRC07-523LS had an estimated elimination half-life of 44 days (41·6-45·7) with a subcutaneous bioavailability of 80·1% (71·4-88·8). Both weight-based and fixed-dose regimens showed similar pharmacokinetic profiles. Observed neutralisation titres were consistent with those predicted on the basis of concentrations and in vitro neutralisation. No treatment-induced anti-drug antibody responses were detected.

Interpretation: The mAb combination of PGDM1400LS, PGT121.414.LS, and VRC07-523LS was safe and well tolerated, with no antagonistic pharmacokinetic interactions or loss of neutralisation activity. These findings support further evaluation of this combination in future efficacy trials.

Fixed dosing versus weight-based dosing of HIV-1 prophylactic monoclonal antibodies in adults: a post-hoc, cross-protocol pharmacokinetics modelling study.

Huang, Y. — EBioMedicine — 2025-07-17

Link: https://pubmed.ncbi.nlm.nih.gov/40516378/

Background: Pharmacokinetic (PK) modelling and simulations have been used to support label changes of dosing levels or strategies for multiple marketed therapeutic monoclonal antibodies (mAbs). Using data from early-phase clinical trials in adults without HIV-1, we compared fixed and weight-based dosing strategies for three HIV-1 broadly neutralising mAbs planned for prevention efficacy evaluation: PGDM1400LS, PGT121.414.LS, and VRC07-523LS.

Methods: We used a two-compartment population PK model to describe overall trends and inter-individual variability in post-administration serum concentrations over time from individuals administered PGDM1400LS (n = 95), PGT121.414.LS (n = 113), or VRC07-523LS (n = 251) subcutaneously or intravenously. We evaluated the effect of body weight on various PK parameters, including clearance rate, and simulated mAb concentrations after fixed and weight-based dosing administrations using sex-specific weights observed in participants from two recent HIV-1 mAb efficacy trials. We compared magnitudes and inter-individual variabilities of concentrations at specific post-administration timepoints, areas under the time-concentration curves (AUC), and predicted neutralisation titres against representative HIV-1 virus strains.

Findings: For all three mAbs, we observed a modest effect of body weight on clearance rate and volumes of the central and peripheral compartments. The population-level magnitude and variability in time-specific concentrations, AUC, and predicted neutralisation titres were comparable between the two dosing strategies for both sexes. The relationship between body weight and concentrations differed between the two dosing strategies with a positive correlation for weight-based dosing and a negative correlation for fixed dosing. For individuals with body weight below the 15th or above the 85th percentiles, fixed dosing resulted in <3% difference in median AUC compared to the overall population. For lower weight individuals, fixed dosing improved AUC, potentially correcting the underdosing seen in the previous weight-based mAb efficacy trials. For higher weight individuals (e.g., >100 kg), body weight-based dosing or a higher fixed dose may be preferred.

Interpretation: For HIV-1 prophylactic mAbs, a fixed-dose approach, possibly banded by weight categories may be advantageous over weight-based dosing, as it offers increased operational efficiency while maintaining comparable pharmacokinetics and inter-individual consistency.

Safety, pharmacokinetics, and neutralisation activity of PGDM1400LS, a V2 specific HIV-1 broadly neutralising antibody, infused intravenously or subcutaneously in people without HIV-1 in the USA (HVTN 140/HPTN 101 part A): a first-in-human, phase 1 randomised trial.

Seaton, K. E. et al. for HVTN 140/HPTN 101 study team — The Lancet HIV — 2025-06-12

Link: https://pubmed.ncbi.nlm.nih.gov/40441807/

Background: PGDM1400LS is a human monoclonal antibody targeting the HIV envelope V2 apex with a lysine-serine modification intended to enhance serum and tissue half-lives and is being considered for use in combination monoclonal antibody trials. We sought to test whether PGDM1400LS was safe and had favourable serum concentration, pharmacokinetics, and neutralising ability in healthy adults.

Methods: HVTN 140/HPTN 101 part A is an open-label, dose escalation, first-in-human phase 1 trial of PGDM1400LS given intravenously or subcutaneously to healthy adults aged 18-50 years without HIV-1. The study enrolled participants at four sites in the USA, across five groups, each receiving one dose of PGDM1400-LS intravenously (group 1: 5 mg/kg; group 2: 20 mg/kg; and group 4: 40 mg/kg) or subcutaneously (group 3: 20 mg/kg; and group 5: 40 mg/kg). Participants in group 1 were enrolled sequentially without random assignment. Participants in groups 2 and 3 were block randomised and enrolled simultaneously after group 1 safety review. Groups 4 and 5 followed the same process, contingent on groups 2 and 3 safety review. The primary endpoints were safety and tolerability of PGDM1400LS, serum concentration of PGDM1400LS, and serum neutralising activity after single administration of PGDM1400LS. Serum PGDM1400LS concentrations collected at seven timepoints (day 0, day 3, day 6, day 28, day 56, day 112, and day 168) were assessed via an anti-idiotype binding assay and characterised via non-compartmental pharmacokinetic analysis. Serum neutralisation activity (ID80) was assessed by a TZM-bl assay. The study is registered with ClinicalTrials.gov, NCT05184452.

Findings: Between Nov 15, 2021, and March 4, 2022, 15 participants were enrolled into the five study groups (three participants per group) with 6 months of follow-up. Ten of 15 participants were female, 14 of 15 participants were non-Hispanic, and 11 of 15 participants were White, with a median age of 27 years (range 24-47). PGDM1400LS was safe and well tolerated, with mild to moderate solicited symptoms. Serum concentrations showed dose proportionality by administration route, with peak concentrations observed immediately after intravenous infusion (range 95·7-727·4 μg/mL) or on day 6 after subcutaneous infusion (205·6-547·1 μg/mL). The median elimination half-life was 55 days (range 48-59), representing a 2-to-3-times increase versus parental PDGM1400. Estimated subcutaneous (vs intravenous) bioavailability was 50-60%. ID80 titres showed agreement with concentration-predicted ID80 titres, indicating maintenance of neutralisation activity in vivo.

Interpretation: PGDM1400LS is a promising candidate for combination monoclonal antibody efficacy trials going forward.

Additional documents

No documents were uploaded

Useful links

There are no additional links