A Clinical Trial of the Safety, Pharmacokinetics and Antiviral Activity of PGT121 Monoclonal Antibody (mAb) in HIV-uninfected and HIV-infected Adults

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
HIV Infection	Biological: PGT121; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))	Phase 1

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

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	63 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Prevention
Official Title:	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
Study Start Date :	November 2016
Estimated Primary Completion Date :	December 2019
Estimated Study Completion Date :	December 2019

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Group 1; HIV-uninfected participants	Biological: PGT121; 3mg/kg administered by IV Infusion; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))
Experimental: Group 2; HIV-uninfected participants	Biological: PGT121; 10mg/kg administered by IV infusion; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))
Experimental: Group 3; HIV-uninfected participants	Biological: PGT121; 30mg/kg administered by IV infusion; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))
Experimental: Group 4; HIV-infected on ART, (<50 cp/ml)	Biological: PGT121; 3mg/kg administered by IV Infusion; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))
Experimental: Group 5; HIV-infected on ART, (<50 cp/ml)	Biological: PGT121; 10mg/kg administered by IV infusion; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))
Experimental: Group 6; HIV-infected on ART, (<50 cp/ml)	Biological: PGT121; 30mg/kg administered by IV infusion; Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))
Experimental: Group 7; HIV-Infected off ART (VL 2x10^3 - 1x10^5 cp/ml)	Biological: PGT121; 30mg/kg administered by IV infusion Placebo: None
Experimental: Group 8; HIV-Infected off ART (VL 2x10^3 - 1x10^5 cp/ml)	Biological: PGT121; 10mg/kg administered by IV infusion Placebo: None
Experimental: Group 9; HIV-Infected off ART (VL 2x10^3 - 1x10^5 cp/ml)	Biological: PGT121; 3mg/kg administered by IV infusion Placebo: None
Experimental: Group 10; HIV-Infected off ART (VL 1x10^2 - 2x10^3 cp/ml)	Biological: PGT121; 30mg/kg administered by IV infusion Placebo: None
Experimental: Group 11; HIV-Infected off ART (VL 1x10^2 - 2x10^3 cp/ml)	Biological: PGT121; 10mg/kg administered by IV infusion Placebo: None
Experimental: Group 12; HIV-Infected off ART (VL 1x10^2 - 2x10^3 cp/ml)	Biological: PGT121; 3mg/kg administered by IV infusion Placebo: None

Outcome Measures

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Primary Outcome Measures :

1. Proportion of participants with PGT121 mAb 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.
2. Impact of viral load and/or ART on PGT121 disposition elimination half-life (t1/2) [ Time Frame: 6 Months post infusion ]
3. Change in plasma HIV-1 RNA levels from baseline (mean of pre-entry and entry values) [ Time Frame: 6 Months post infusion ]
4. Impact of viral load and/or ART on PGT121 disposition clearance (CL/F) [ Time Frame: 6 Months post infusion ]
5. Impact of viral load and/or ART on PGT121 disposition volume of distribution (Vz/F) [ Time Frame: 6 months post infusion ]
6. Impact of viral load and/or ART on PGT121 disposition total exposure [ Time Frame: 6 months post infusion ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 50 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Group 1 Inclusion Criteria:

• 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 on a stable antiretroviral regimen with HIV-1 RNA plasma level <50 copies/ml, CD4 cell count > 300 cells/uL and CD4 nadir > 200 cell/uL

Group 2 Exclusion Criteria:

• history of AIDS-defining illness, significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities

Group 3 Inclusion Criteria:

• HIV-infected males or females not on antiretroviral therapy for > 6 month with detectable HIV-1 RNA plasma level between 100 and 100,000 copies/ml, CD4 cell count > 300 cells/uL and CD4 nadir > 200 cell/uL

Group 3 Exclusion Criteria:

• history of AIDS-defining illness, significant acute or chronic medical condition other than HIV infection, and clinically significant laboratory abnormalities

Contacts and Locations

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Locations

United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

International AIDS Vaccine Initiative

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

Investigators

Principal Investigator:	Kathryn Stephenson, MD MPH	Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research
Study Chair:	Boris Juelg, MD PhD	Ragon Institute

More Information

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Additional Information:

International AIDS Vaccine Initiative 

Responsible Party:	International AIDS Vaccine Initiative
ClinicalTrials.gov Identifier:	NCT02960581 History of Changes
Other Study ID Numbers:	IAVI T001
First Posted:	November 9, 2016
Last Update Posted:	January 3, 2019
Last Verified:	January 2019

Additional relevant MeSH terms:

HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes	Immune System Diseases; Antibodies; Antibodies, Monoclonal; Antiviral Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Infective Agents