HIV Infection
Conditions
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.
Interventions
BIOLOGICALPGT121 3mg/kg IV
3mg/kg administered by IV Infusion
BIOLOGICALPGT121 10mg/kg IV
10mg/kg administered by IV infusion
BIOLOGICALPGT121 30mg/kg IV
30mg/kg administered by IV infusion
BIOLOGICALPGT121 3mg/kg SC
3mg/kg administered by SC injection Placebo: None
BIOLOGICALPlacebo (0.9% Sodium Chloride Injection USP (Saline))
Sponsors
Beth Israel Deaconess Medical Center, Boston MA
Ragon Institute of MGH, MIT and Harvard, Boston MA
University of Texas Health, Houston AIDS Research Team (HART), Houston TX
Mills Clinical Research, Los Angeles CA
Orlando Immunology Clinic, Orlando FL
International AIDS Vaccine Initiative
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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: 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) |
| 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) |
Countries
United States
Outcome results
None listed