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

Phase 1

Completed

• Conditions: HIV/AIDS
• Interventions: Biological: PGT121 + VRC07-523LS + PGDM1400; Biological: PGT121 + VRC07-523LS

• Registration Number: NCT03721510
• Lead Sponsor: International AIDS Vaccine Initiative

Brief Summary

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.

Detailed Description

This is a Phase 1/2a open label study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of PGT121, VRC07-523LS and PGDM1400 antibodies for HIV prevention and therapy. PGT121, VRC07-523LS and PGDM1400 are recombinant human IgG1 monoclonal antibodies that target a V3 glycan-dependent epitope region of the HIV envelope protein and the CD4 binding site (CD4bs) of the HIV envelope protein. PGT121, VRC07-523LS and PGDM1400 mAbs were chosen for this study because of their potency, their ability to neutralize a wide array of cross-clade HIV viruses in a complementary pattern, and their proven antiviral activity in animal studies, e.g., their capacity to robustly prevent and treat simian-human immunodeficiency virus (SHIV) in rhesus monkeys.

The potency and breadth of PGT121, VRC07-523LS and PGDM1400 raise the possibility that monoclonal antibodies may be effective for HIV prophylaxis at low doses and against global viruses. Neutralization sensitivity profiles are complementary; and the combination of these mAbs with unique epitope specificities will provide experience assessing the potential additive, synergistic, or antagonistic properties of two bNAbs given sequentially.

Study Timeline

• Study First Submitted: 2018-03-16
• Study First Submitted QC: 2018-10-24
• Study First Posted: 2018-10-26
• Study Start: 2018-12-03
• Primary Completion: 2021-10-25
• Status Verified: 2022-05
• Study Completion: 2022-05-02
• Last Update Submitted: 2022-05-06
• Last Update Posted: 2022-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1B	PGT121 + VRC07-523LS + PGDM1400	HIV-uninfected volunteers receiving one IV infusion
Group 1A	PGT121 + VRC07-523LS	HIV-uninfected volunteers receiving one IV infusion
Group 2	PGT121 + VRC07-523LS + PGDM1400	HIV-infected volunteers on ART receiving three or six IV infusions

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics - Area under the concentration decay curve (AUC)	Up to 44 weeks	Pharmacokinetics following IV infusion of PGT121, VRC07-523LS and PGDM1400 in HIV-uninfected and HIV-infected adults: • Area under the concentration decay curve (AUC)
Safety and Tolerability - Proportion of volunteers with moderate or greater reactogenicity	3 days post infusion for each infusion	Proportion of volunteers with moderate or greater reactogenicity (i.e., solicited adverse events) for 3 days following each IV infusion of PGT121, VRC07-523LS and PGDM1400 as assessed using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, July 2017, or the Common Terminology Criteria for Adverse Events (CTCAE,) Version 5.0 27 November 2017 (for reactogenicity observed within the first 24 hours post-infusion.)
Safety and Tolerability - Proportion of volunteers with serious adverse events (SAEs)	Up to 44 weeks	Proportion of volunteers with serious adverse events (SAEs) throughout the study period following IV infusion(s) of PGT121, VRC07-523LS and PGDM1400 that are considered related to PGT121 and/or VRC07-523LS and/or PGDM1400 as assessed using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, or the Common Terminology Criteria for Adverse Events (CTCAE,) Version 5.0 27 November 2017 (for reactogenicity observed within the first 24 hours post-infusion.)
Safety and Tolerability - Proportion of volunteers with adverse events (AEs)	56 days	Proportion of volunteers with adverse events (AEs), including safety laboratory (biochemical, hematological) parameters, during the 56 days following IV infusion of PGT121, VRC07-523LS and PGDM1400 that are moderate or greater, and/or considered related to PGT121 and/or VRC07-523LS and/or PGDM1400 as assessed using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, or the Common Terminology Criteria for Adverse Events (CTCAE,) Version 5.0 27 November 2017 (for reactogenicity observed within the first 24 hours post-infusion.)
Pharmacokinetics - Elimination half-life (t1/2)	Up to 44 weeks	Pharmacokinetics following IV infusion of PGT121, VRC07-523LS and PGDM1400 in HIV-uninfected and HIV-infected adults: • Elimination half-life (t1/2)
Pharmacokinetics - Volume of distribution (Vz/F)	Up to 44 weeks	Pharmacokinetics following IV infusion of PGT121, VRC07-523LS and PGDM1400 in HIV-uninfected and HIV-infected adults: • Volume of distribution (Vz/F)
Pharmacokinetics - Clearance (CL/F)	Up to 44 weeks	Pharmacokinetics following IV infusion of PGT121, VRC07-523LS and PGDM1400 in HIV-uninfected and HIV-infected adults: • Clearance (CL/F)

Secondary Outcome Measures

Name	Time	Method
Anti-PGDM1400 antibodies	Up to 44 weeks	Serum anti-PGDM1400 antibody titers
Anti-VRC07-523LS antibodies	Up to 44 weeks	Serum anti-VRC07-523LS antibody titers
Antiviral Activity - Time to meeting ART re-initiation criteria	Up to 44 weeks	Time to meeting ART re-initiation criteria (plasma HIV-1 RNA level ≥ 1000 copies/ml, CD4+ T cell count \< 300 cells/ μl in two consecutive measurements) following ART interruption in Group 2
Antiviral Activity - Proportion of volunteers who meet ART re-initiation criteria	Up to 44 weeks	Proportion of volunteers who meet ART re-initiation criteria (defined as plasma HIV-1 RNA ≥ 1000 copies/ml and/or CD4 count \< 300 cells/μl) on two consecutive measurements following ART interruption in Group 2
mAb serum levels at the time of viral rebound in Group 2	Up to 44 weeks	Serum levels of PGDM1400 at time of viral rebound
CD4+ T cell count	Up to 44 weeks	Change in CD4+ T cell count and frequency compared to baseline as measured by single platform flow cytometry in HIV-infected adults following IV infusion of PGT121, VRC07-523LS and PGDM1400.
Effects of PGT121, VRC07-523LS and PGDM1400 on viral escape mutations in rebound viruses	Up to 44 weeks	Phylogenetic comparison of viruses grown from PBMCs collected from volunteers while on ART to rebound viruses collected after ART interruption (Group 2)
Anti-PGT121 antibodies	Up to 44 weeks	Serum anti-PGT121 antibody titers

Trial Locations

Locations (3)

Center for Virology and Vaccine Research/ Clinical Trials Unit/ BIDMC; 🇺🇸 Boston, Massachusetts, United States

Orlando Immunology Center; 🇺🇸 Orlando, Florida, United States

Houston AIDS Research Team (HART); 🇺🇸 Houston, Texas, United States