PGT121.414.LS / National Institute of Allergy and Infectious Diseases - LARVOL DELTA

A Study to Evaluate the Safety and Antiviral Activity of Two Human Monoclonal Antibodies (VRC07-523LS and PGT121.414.LS) During Analytic Treatment Interruption in Participants Living With HIV Who Initiated ART During Acute/Early HIV-1 Infection (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Initiation date: Oct 2025 ➔ Feb 2026

Trial initiation date • Human Immunodeficiency Virus • Infectious Disease

Proteoform Characterization of HIV-1 Broadly Neutralizing Antibody PGT 121.414.LS Product Through Middle-Up and Bottom-Up Proteomics for Clinical Support. (PubMed, J Am Soc Mass Spectrom) - "For Fd, bottom-up analysis revealed eight sialylated glycoforms and five nonsialylated glycoforms at Asn-124 of the heavy chain. The results emphasize bNAb heterogeneity, which should be considered in affinity binding studies."

Journal • Human Immunodeficiency Virus • Infectious Disease

A Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Suspended ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease • CD4

LC-MS/MS method for quantifying the HIV-1 broadly neutralizing antibody PGT 121.414.LS in human serum. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "The method exhibits minimal carryover and negligible crosstalk. The assay provides accurate quantification of PGT 121.414.LS in serum over the range of concentrations anticipated in specimens from treated persons living with HIV (PLWH) after initial dosing and prior to subsequent dosing of PGT 121.414.LS."

Journal • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease

A Study to Evaluate the Safety and Antiviral Activity of Two Human Monoclonal Antibodies (VRC07-523LS and PGT121.414.LS) During Analytic Treatment Interruption in Participants Living With HIV Who Initiated ART During Acute/Early HIV-1 Infection (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Initiation date: Jun 2025 ➔ Oct 2025

Trial initiation date • 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

A Study to Evaluate the Safety and Antiviral Activity of Two Human Monoclonal Antibodies (VRC07-523LS and PGT121.414.LS) During Analytic Treatment Interruption in Participants Living With HIV Who Initiated ART During Acute/Early HIV-1 Infection (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

A Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission (clinicaltrials.gov) - P2 | N=48 | Suspended | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Suspended

Trial suspension • Human Immunodeficiency Virus • Infectious Disease • CD4

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

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

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

Safety and Pharmacokinetics Study of PGT121.414.LS Alone and in Combination With VRC07-523LS in Infants Exposed to HIV-1 (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Nov 2027 ➔ Jun 2028 | Initiation date: Nov 2024 ➔ Jun 2025 | Trial primary completion date: May 2026 ➔ Dec 2027

Trial completion date • Trial initiation date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

A Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial primary completion date: Sep 2025 ➔ Apr 2028

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Safety, tolerability, pharmacokinetics, and neutralisation activities of the anti-HIV-1 monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS in adults without HIV in the USA (HVTN 136/HPTN 092): a first-in-human, open-label, randomised controlled phase 1 trial. (PubMed, Lancet HIV) - P1 | "These findings support further evaluation of PGT121.414.LS in combination with other mAbs for HIV-1 prevention."

Combination therapy • Journal • P1 data • PK/PD data • Allergy • Human Immunodeficiency Virus • Immunology • 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

Pharmacokinetic interaction assessment of the HIV broadly neutralizing monoclonal antibody VRC07-523LS: a cross-protocol analysis of three phase 1 HIV prevention trials HVTN127/HPTN087, HVTN130/HPTN089 and HVTN136/HPTN092 (HIVR4P 2024) - "We included participants receiving intravenous or subcutaneous VRC07-523LS alone (HVTN127/HPTN087, n=100), combined with PGT121, PGDM1400 or 10-1074 (HVTN130/HPTN089, n=26), or combined with PGT121.414.LS (HVTN136/HPTN092, n=20). Biodistribution of VRC07-523LS differed when administered combined with other mAbs versus alone, but overall concentration-over-time was not impacted. This is important for planning future trials of VRC07-523LS with new mAb formulations."

Clinical • P1 data • PK/PD 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

A Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease • CD4

Safety and Pharmacokinetics Study of PGT121.414.LS Alone and in Combination With VRC07-523LS in Infants Exposed to HIV-1 (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Combination therapy • New P1 trial • Human Immunodeficiency Virus • Infectious Disease

A first-in-human phase 1 trial of PGT121.414.LS administered alone and in combination with VRC07-523LS: safety, tolerability, pharmacokinetics, and neutralization activity (HVTN 136/HPTN 092) (AIDS 2024) - "First-in-human IV or SC infusions n of PGT121.414.LS were safe and well-tolerated, alone or in combination with VRC07-523LS. These findings support additional evaluations of PGT121.414.LS in combination with other mAbs for HIV-1 prevention."

Clinical • Combination therapy • 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