A Phase 1 Randomized Placebo-controlled Clinical Trial of the Safety, Pharmacokinetics and Antiviral Activity of PGT121 Monoclonal Antibody (mAb) in HIV-uninfected and HIV-infected Adults
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 48
- Locations
- 2
- Primary Endpoint
- Pharmacokinetics: elimination half-life (t1/2)
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •HIV-uninfected males or females age 18-50 years old
- •Willing to maintain low risk behavior for HIV infection
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
Arms & Interventions
Group 1C
HIV-uninfected participants
Intervention: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
Group 1C
HIV-uninfected participants
Intervention: PGT121 30mg/kg IV (Biological)
Group 2A
HIV-infected on ART, (<50 cp/ml)
Intervention: PGT121 3mg/kg IV (Biological)
Group 1A
HIV-uninfected participants
Intervention: PGT121 3mg/kg IV (Biological)
Group 1A
HIV-uninfected participants
Intervention: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
Group 1B
HIV-uninfected participants
Intervention: PGT121 10mg/kg IV (Biological)
Group 1B
HIV-uninfected participants
Intervention: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
Group 2A
HIV-infected on ART, (<50 cp/ml)
Intervention: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
Group 2B
HIV-infected on ART, (<50 cp/ml)
Intervention: PGT121 10mg/kg IV (Biological)
Group 2B
HIV-infected on ART, (<50 cp/ml)
Intervention: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
Group 2C
HIV-infected on ART, (<50 cp/ml)
Intervention: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
Group 2C
HIV-infected on ART, (<50 cp/ml)
Intervention: PGT121 30mg/kg IV (Biological)
Group 3A
HIV-Infected off ART (VL 2x10^3 - 1x10^5 cp/ml)
Intervention: PGT121 30mg/kg IV (Biological)
Group 3B
HIV-Infected off ART (VL 1x10^2 - 2x10^3 cp/ml)
Intervention: PGT121 30mg/kg IV (Biological)
Arm 1D
HIV-uninfected participants
Intervention: PGT121 3mg/kg SC (Biological)
Arm 1D
HIV-uninfected participants
Intervention: Placebo (0.9% Sodium Chloride Injection USP (Saline)) (Biological)
Outcomes
Primary Outcomes
Pharmacokinetics: elimination half-life (t1/2)
Time Frame: 6 Months post infusion
Pharmacokinetics: elimination half-life (t1/2)
Pharmacokinetics: Clearance (CL/F)
Time Frame: 6 Months post infusion
Pharmacokinetics: Clearance (CL/F)
Pharmacokinetics: Volume of distribution (Vz/F)
Time Frame: 6 months post infusion
Pharmacokinetics: Volume of distribution (Vz/F)
Pharmacokinetics: Area under the concentration decay curve (AUC)
Time Frame: 6 months post infusion
Pharmacokinetics: Area under the concentration decay curve (AUC)
Proportion of participants with PGT121 mAb reactogenicity, related AEs and SAEs
Time Frame: 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
Time Frame: 6 months post infusion
Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure
Antiviral Activity
Time Frame: 6 Months post infusion
Change in plasma HIV-1 RNA levels from baseline (mean of pre-entry and entry values)
Secondary Outcomes
No secondary outcomes reported