Safety, PK and Antiviral Activity of PGT121 Monoclonal Antibody in HIV-uninfected and HIV-infected Adults

International AIDS Vaccine Initiative48 enrolled

Overview

This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGT121 monoclonal antibody for HIV prevention and therapy.

This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and anti-viral efficacy of the PGT121 monoclonal antibody for HIV prevention and therapy. PGT121 mAb is a recombinant human IgG1 monoclonal antibody that targets a V3 glycan-dependent epitope region of the HIV envelope protein. PGT121 mAb was chosen for this study because it is potent, neutralizes a wide array of HIV viruses, and can prevent and treat simian-human immunodeficiency virus (SHIV) in rhesus monkeys.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

Conditions

HIV Infection

Interventions

PGT121 3mg/kg IVBIOLOGICAL

3mg/kg administered by IV Infusion

PGT121 10mg/kg IVBIOLOGICAL

10mg/kg administered by IV infusion

PGT121 30mg/kg IVBIOLOGICAL

30mg/kg administered by IV infusion

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Group 1 Inclusion Criteria: * HIV-uninfected males or females age 18-50 years old * Willing to maintain low risk behavior for HIV infection Group 1 Exclusion Criteria: * confirmed HIV-infection, pregnancy or lactation, significant acute or chronic disease and clinically significant laboratory abnormalities Group 2 Inclusion Criteria: * HIV-infected males or females age 18-65 years old * On a stable antiretroviral regimen with HIV-1 RNA plasma level \<50 copies/ml, CD4 cell count greater than or equal to 300 cells/uL Group 2 Exclusion Criteria: * history of AIDS-defining illness within the previous 5 years, significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities Group 3 Inclusion Criteria: * HIV-infected males or females age 18-65 * Not on antiretroviral therapy for \> 6 months with detectable HIV-1 viral load between 100 and 100,000 copies/ml, CD4 cell count greater than or equal to 300 cells/uL Group 3 Exclusion Criteria: * history of AIDS-defining illness within the previous 5 years, significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities

Locations (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

Proportion of participants with PGT121 mAb reactogenicity, related AEs and SAEs

The investigators will measure the following endpoints to evaluate the safety and tolerability of PGT121 mAb in HIV-uninfected and HIV-infected adults: 1. Proportion of participants with moderate or greater reactogenicity (e.g., solicited adverse events) for 3 days following IV infusion of PGT121 mAb. 2. Proportion of participants with moderate or greater and/or PGT121 mAb-related unsolicited adverse events (AEs), including safety laboratory (biochemical, hematological) parameters, following IV infusion of PGT121 mAb for the first 56 days post administration of Investigational Product. 3. Proportion of participants with PGT121 mAb-related serious adverse events (SAEs) throughout the study period.

Time frame: 6 Months post infusion

Pharmacokinetics: elimination half-life (t1/2)

Time frame: 6 Months post infusion

Pharmacokinetics: Clearance (CL/F)

Time frame: 6 Months post infusion

Pharmacokinetics: Volume of distribution (Vz/F)

Time frame: 6 months post infusion

Pharmacokinetics: Area under the concentration decay curve (AUC)

Time frame: 6 months post infusion

Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure

Time frame: 6 months post infusion

Data from ClinicalTrials.gov

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