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

Phase 1

Completed

• Conditions: HIV Infection
• Interventions: Biological: PGT121 10mg/kg IV; Biological: PGT121 30mg/kg IV; Biological: PGT121 3mg/kg SC; Biological: PGT121 3mg/kg IV; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))

• Registration Number: NCT02960581
• Lead Sponsor: International AIDS Vaccine Initiative

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2016-10-18
• Study Start: 2016-11
• Study First Submitted QC: 2016-11-07
• Study First Posted: 2016-11-09
• Primary Completion: 2019-07-08
• Study Completion: 2019-07-08
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-13
• Last Update Posted: 2019-09-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

• HIV-uninfected males or females age 18-50 years old
• Willing to maintain low risk behavior for HIV infection

Group 1

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1D	Placebo (0.9% Sodium Chloride Injection USP (Saline))	HIV-uninfected participants
Group 1B	PGT121 10mg/kg IV	HIV-uninfected participants
Group 1C	PGT121 30mg/kg IV	HIV-uninfected participants
Group 1A	Placebo (0.9% Sodium Chloride Injection USP (Saline))	HIV-uninfected participants
Group 2C	Placebo (0.9% Sodium Chloride Injection USP (Saline))	HIV-infected on ART, (\<50 cp/ml)
Arm 1D	PGT121 3mg/kg SC	HIV-uninfected participants
Group 1C	Placebo (0.9% Sodium Chloride Injection USP (Saline))	HIV-uninfected participants
Group 1A	PGT121 3mg/kg IV	HIV-uninfected participants
Group 1B	Placebo (0.9% Sodium Chloride Injection USP (Saline))	HIV-uninfected participants
Group 2A	PGT121 3mg/kg IV	HIV-infected on ART, (\<50 cp/ml)
Group 2A	Placebo (0.9% Sodium Chloride Injection USP (Saline))	HIV-infected on ART, (\<50 cp/ml)
Group 2C	PGT121 30mg/kg IV	HIV-infected on ART, (\<50 cp/ml)
Group 2B	PGT121 10mg/kg IV	HIV-infected on ART, (\<50 cp/ml)
Group 2B	Placebo (0.9% Sodium Chloride Injection USP (Saline))	HIV-infected on ART, (\<50 cp/ml)
Group 3A	PGT121 30mg/kg IV	HIV-Infected off ART (VL 2x10\^3 - 1x10\^5 cp/ml)
Group 3B	PGT121 30mg/kg IV	HIV-Infected off ART (VL 1x10\^2 - 2x10\^3 cp/ml)

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics: elimination half-life (t1/2)	6 Months post infusion	Pharmacokinetics: elimination half-life (t1/2)
Pharmacokinetics: Clearance (CL/F)	6 Months post infusion	Pharmacokinetics: Clearance (CL/F)
Pharmacokinetics: Volume of distribution (Vz/F)	6 months post infusion	Pharmacokinetics: Volume of distribution (Vz/F)
Pharmacokinetics: Area under the concentration decay curve (AUC)	6 months post infusion	Pharmacokinetics: Area under the concentration decay curve (AUC)
Proportion of participants with PGT121 mAb reactogenicity, related AEs and SAEs	6 Months post infusion	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.
Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure	6 months post infusion	Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure
Antiviral Activity	6 Months post infusion	Change in plasma HIV-1 RNA levels from baseline (mean of pre-entry and entry values)

Trial Locations

Locations (1)

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States