PGDM1400LS / National Institute of Allergy and Infectious Diseases - LARVOL DELTA

RV630 - Approach to Control HIV With Immune Enhancement and Vaccination (ACHIEV (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine | Active, not recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

RV630 - Approach to Control HIV With Immune Enhancement and Vaccination (ACHIEV (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

A randomized, double-blind, controlled, phase 2 clinical trial to evaluate safety, tolerability, pharmacokinetics, and neutralization of VRC07-523LS, PGT121.414.LS, and PGDM1400LS broadly neutralizing monoclonal antibodies given intravenously in adults without HIV (IAS-HIV 2025) - "HVTN206/HPTN114 represents a critical step in advancing HIV prevention strategies by testing a triple-bnAb combination informed by robust evidence from the AMP efficacy trials and phase 1 trials with next-generation bnAbs, including HVTN140/HPTN101 with the same triple-bnAb combination. This trial will inform the design of the combo-AMP efficacy trials and could establish HIV bnAbs immunoprophylaxis (passive immunization) as a biannual, long-acting option for HIV prevention, addressing key gaps in current strategies and enhancing global HIV prevention programs."

Clinical • P2 data • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

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

Journal • PK/PD data • Retrospective data • Human Immunodeficiency Virus • Infectious Disease

The Tatelo Plus Study (clinicaltrials.gov) - P1/2 | N=41 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial primary completion date: Feb 2028 ➔ Nov 2027

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

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. (PubMed, Lancet HIV) - P1 | "PGDM1400LS is a promising candidate for combination monoclonal antibody efficacy trials going forward."

Clinical • Journal • P1 data • PK/PD data • Allergy • Human Immunodeficiency Virus • Immunology • Infectious Disease

A Study of VRC07-523LS, PGT121.414.LS, and PGDM1400LS Broadly Neutralizing Monoclonal Antibodies Given Intravenously in Adult Participants Without HIV (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Maximizing Benefits to Participants in Analytic Treatment Interruption With Antibody Infusions (CROI 2025) - "Neutralization data from 116 participants showed 54 (46.5%) sensitive to PGDM1400LS, 55 (46.7%) sensitive to VRC07-523LS, and 25 (21.5%) sensitive to both. We also modeled the Instantaneous Inhibitory Potential (IIP) values; at week 20 post ATI, 75 participants had clones with IIP (PGDM1400 + VRC07)>3.5, allowing prioritization of participants for study enrolment...Our approach benefitted from the fact that participants initiated ART in acute infection and therefore had a typically homogeneous viral reservoir recapitulated by the limited number of distinct env sequences we sampled. While the benefits of this approach will only be ascertained after the ATI is conducted, these data provide the largest description of sensitivity to two potent bnAbs across CRF01_AE viruses."

Human Immunodeficiency Virus • Infectious Disease

Sensitivity of HIV-1 CRF01_AE Envelopes to Broadly Neutralizing Antibodies VRC07-523 and PGDM1400 (CROI 2025) - "Background Understanding the sensitivity of viral envelopes to broadly neutralizing antibodies (bNAbs) encoded within the reservoir is of major importance in evaluating efficacy in analytical treatment interruption (ATI) trials using bNAbs as an intervention in people living with HIV (PLWH). Combining VRC07-523LS and PGDM1400LS bNAbs provided increased coverage across viral Envs. Furthermore, PGDM1400LS demonstrated more potent neutralization across the screened candidates and required lower concentrations to achieve a higher level of viral inhibition in comparison to VRC07-523LS. These data provide evidence that CRF01_AE Envs sequenced from viral Env are sensitive to VRC07-523LS and PGDM1400LS and antibodies may be used as candidate bNAbs in future ATI trials."

Human Immunodeficiency Virus • Infectious Disease • CD4

Fixed Dosing Versus Body-Weight-Based Dosing of HIV-1 Prophylactic Monoclonal Antibodies in Adults (CROI 2025) - "We aimed to evaluate fixed dosing versus weight-based dosing for 3 IgG1-based HIV-1 mAbs, VRC07-523LS, PGT121.414.LS and PGDM1400LS, that are planned for HIV-1 prevention efficacy testing, based on data from earlier clinical trials of these mAbs in people without HIV-1. For individuals with body weight below the 15th or above the 85th percentiles, fixed dosing results in < 3% difference in median AUC compared to the overall population. Conclusions Given the advantage of fixed dosing in reducing vial wastage and increasing operational efficiency, fixed dosing is recommended for these 3 HIV-1 mAbs in future clinical testing."

Clinical • Human Immunodeficiency Virus • Infectious Disease

Use of broadly neutralizing antibodies in pediatric HIV for treatment and remission. (PubMed, Curr Opin HIV AIDS) - "This review synthesizes data for ongoing and planned pediatric bNAb treatment studies, focusing on available trial results that underscore the ability of newer and more potent long-acting bNAbs to sustain viral suppression. We discuss the potential impact of bNAbs to reduce the latent viral reservoir and their use as a strategy to achieve viral remission in children with HIV."

Journal • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

A Study of VRC07-523LS, PGT121.414.LS, and PGDM1400LS Broadly Neutralizing Monoclonal Antibodies Given Intravenously in Adult Participants Without HIV (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

New P2 trial • Human Immunodeficiency Virus • Infectious Disease

The Tatelo Plus Study (clinicaltrials.gov) - P1/2 | N=41 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease • CD4

Acceptability of intravenous (IV) and subcutaneous (SC) infusion administration of monoclonal antibody (mAb) combinations: VRC07-523LS with PGT121, PGDM1400, PGT121.414.LS and PGDM1400LS in phase 1 anti-HIV mAb trials (HIVR4P 2024) - "Participants consistently chose the route of administration that was used during study participation (IV or SC) or IM injection as their method of HIV prevention. Additionally, opinions of infusion visit time and recommendation of their route of administration was not different after the first and last administrations. These data support consideration for multiple routes of mAb administration appropriate for the volumes and doses needed for HIV prevention."

Late-breaking abstract • P1 data • Human Immunodeficiency Virus • Infectious Disease

Phase 1 dose-escalation trial to evaluate the safety, tolerability, pharmacokinetics and neutralization activity of PGDM1400LS in combination with VRC07-523LS and PGT121.414.LS in healthy participants without HIV (HVTN 140/HPTN 101) (HIVR4P 2024) - "The bNAb combination of PGDM1400LS, PGT121.414.LS, and VRC07-523LS was safe and well-tolerated, with no pharmacokinetic interactions or loss of complementary neutralization. These findings strongly support the evaluation of this triple combination in future efficacy trials."

Clinical • Combination therapy • Late-breaking abstract • P1 data • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • CD4

Assessment of infusion-related reactions after intravenous administration of HIV monoclonal antibodies PGT121.414.LS, PGDM1400.LS or VRC07-523LS (alone or in combination with PGT121, PGDM1400, 10-1074, PGT121.414.LS, PGDM1400.LS), in five phase 1 studies (HIVR4P 2024) - "IRRs after IV administration of anti-HIV mAbs in these trials were uncommon, mild to moderate, and most were self-limited. These findings support the safe administration of these mAbs combinations by IV infusions in future HIV prevention clinical trials."

Combination therapy • Late-breaking abstract • P1 data • Fatigue • Human Immunodeficiency Virus • Infectious Disease • Musculoskeletal Pain • Pain

First-in-human evaluation of the safety, pharmacokinetics, and neutralization activity of PGDM1400-LS, a V2 glycan-specific HIV-1 broadly neutralizing antibody, infused intravenously or subcutaneously in people without HIV-1 (HVTN140/HPTN101 Part A) (AIDS 2024) - "Intravenously-administered PGDM1400-LS exhibits favorable pharmacokinetics in vivo and is a promising candidate for future efficacy trials."

Clinical • P1 data • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

The Tatelo Plus Study (clinicaltrials.gov) - P1/2 | N=41 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

New P1/2 trial • Human Immunodeficiency Virus • Infectious Disease • CD4

ACHIEV: Safety and Efficacy of Broadly Neutralizing Antibodies Combined With Therapeutic Vaccination for the Induction of HIV Remission (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

HVTN143: Evaluating the Safety, Tolerability, and Pharmacokinetics of Monoclonal Antibodies in Healthy Participants (clinicaltrials.gov) - P1 | N=77 | Suspended | Sponsor: HIV Vaccine Trials Network | Not yet recruiting ➔ Suspended

Trial suspension • Human Immunodeficiency Virus • Infectious Disease

Impact of LS Mutation on Pharmacokinetics of Preventive HIV Broadly Neutralizing Monoclonal Antibodies: A Cross-Protocol Analysis of 16 Clinical Trials in People without HIV. (PubMed, Pharmaceutics) - "To characterize the LS mutation for monoclonal antibodies targeting HIV, we compared pharmacokinetic parameters between parental versus LS variants for five pairs of anti-HIV immunoglobin G1 monoclonal antibodies (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS PGT121/LS, 10-1074/LS), analyzing data from 16 clinical trials of 583 participants without HIV. Results suggest a favorable pharmacokinetic profile of LS variants regardless of HIV epitope specificity. Insights support lower dosages and/or less frequent dosing of LS variants to achieve similar levels of antibody exposure in future clinical applications."

Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

RV582: Safety and Efficacy of Neutralizing Antibodies and Vaccination for Induction of HIV Remission (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine | N=35 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Human Immunodeficiency Virus • Infectious Disease • CD4

HVTN143: Evaluating the Safety, Tolerability, and Pharmacokinetics of Monoclonal Antibodies in Healthy Participants (clinicaltrials.gov) - P1 | N=77 | Not yet recruiting | Sponsor: HIV Vaccine Trials Network | Initiation date: Oct 2023 ➔ Apr 2024

Trial initiation date • Human Immunodeficiency Virus • Infectious Disease

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 (clinicaltrials.gov) - P1 | N=95 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Human Immunodeficiency Virus • Infectious Disease

HVTN143: Evaluating the Safety, Tolerability, and Pharmacokinetics of Monoclonal Antibodies in Healthy Participants (clinicaltrials.gov) - P1 | N=77 | Not yet recruiting | Sponsor: HIV Vaccine Trials Network

New P1 trial • Human Immunodeficiency Virus • Infectious Disease