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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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HIV Infection

Intervention / Treatment
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* Biological: PGT121 3mg/kg IV
* Biological: PGT121 10mg/kg IV
* Biological: PGT121 30mg/kg IV
* Biological: PGT121 3mg/kg SC
* Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1A<br>HIV-uninfected participants | Biological: PGT121 3mg/kg IV<br>* 3mg/kg administered by IV Infusion<br>Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))<br> <br> |
| Experimental: Group 1B<br>HIV-uninfected participants | Biological: PGT121 10mg/kg IV<br>* 10mg/kg administered by IV infusion<br>Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))<br> <br> |
| Experimental: Group 1C<br>HIV-uninfected participants | Biological: PGT121 30mg/kg IV<br>* 30mg/kg administered by IV infusion<br>Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))<br> <br> |
| Experimental: Group 2A<br>HIV-infected on ART, (<50 cp/ml) | Biological: PGT121 3mg/kg IV<br>* 3mg/kg administered by IV Infusion<br>Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))<br> <br> |
| Experimental: Group 2B<br>HIV-infected on ART, (<50 cp/ml) | Biological: PGT121 10mg/kg IV<br>* 10mg/kg administered by IV infusion<br>Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))<br> <br> |
| Experimental: Group 2C<br>HIV-infected on ART, (<50 cp/ml) | Biological: PGT121 30mg/kg IV<br>* 30mg/kg administered by IV infusion<br>Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))<br> <br> |
| Experimental: Group 3A<br>HIV-Infected off ART (VL 2x10^3 - 1x10^5 cp/ml) | Biological: PGT121 30mg/kg IV<br>* 30mg/kg administered by IV infusion<br>|
| Experimental: Group 3B<br>HIV-Infected off ART (VL 1x10^2 - 2x10^3 cp/ml) | Biological: PGT121 30mg/kg IV<br>* 30mg/kg administered by IV infusion<br>|
| Experimental: Arm 1D<br>HIV-uninfected participants | Biological: PGT121 3mg/kg SC<br>* 3mg/kg administered by SC injection Placebo: None<br>Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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: Proportion of participants with moderate or greater reactogenicity (e.g., solicited adverse events) for 3 days following IV infusion of PGT121 mAb. 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. Proportion of participants with PGT121 mAb-related serious adverse events (SAEs) throughout the study period. | 6 Months post infusion | 
| Pharmacokinetics: elimination half-life (t1/2) | Pharmacokinetics: elimination half-life (t1/2) | 6 Months post infusion | 
| Pharmacokinetics: Clearance (CL/F) | Pharmacokinetics: Clearance (CL/F) | 6 Months post infusion | 
| Pharmacokinetics: Volume of distribution (Vz/F) | Pharmacokinetics: Volume of distribution (Vz/F) | 6 months post infusion | 
| Pharmacokinetics: Area under the concentration decay curve (AUC) | Pharmacokinetics: Area under the concentration decay curve (AUC) | 6 months post infusion | 
| Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure | Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure | 6 months post infusion | 
| Antiviral Activity | Change in plasma HIV-1 RNA levels from baseline (mean of pre-entry and entry values) | 6 Months post infusion |