A Phase 1/2a Open Label Study of the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of PGT121, VRC07-523LS and PGDM1400 Monoclonal Antibodies in HIV-uninfected and HIV-infected Adults
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV/AIDS
- Sponsor
- International AIDS Vaccine Initiative
- Enrollment
- 19
- Locations
- 3
- Primary Endpoint
- Pharmacokinetics - Area under the concentration decay curve (AUC)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Pharmacokinetics - Area under the concentration decay curve (AUC)
Time Frame: 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
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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 Outcomes
- Anti-PGDM1400 antibodies(Up to 44 weeks)
- Anti-VRC07-523LS antibodies(Up to 44 weeks)
- Antiviral Activity - Time to meeting ART re-initiation criteria(Up to 44 weeks)
- Antiviral Activity - Proportion of volunteers who meet ART re-initiation criteria(Up to 44 weeks)
- mAb serum levels at the time of viral rebound in Group 2(Up to 44 weeks)
- CD4+ T cell count(Up to 44 weeks)
- Effects of PGT121, VRC07-523LS and PGDM1400 on viral escape mutations in rebound viruses(Up to 44 weeks)
- Anti-PGT121 antibodies(Up to 44 weeks)