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

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

9

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: International AIDS Vaccine Initiative
• Collaborators: 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

Publications and helpful links

General Publications

• Stephenson KE, Julg B, Tan CS, Zash R, Walsh SR, Rolle CP, Monczor AN, Lupo S, Gelderblom HC, Ansel JL, Kanjilal DG, Maxfield LF, Nkolola J, Borducchi EN, Abbink P, Liu J, Peter L, Chandrashekar A, Nityanandam R, Lin Z, Setaro A, Sapiente J, Chen Z, Sunner L, Cassidy T, Bennett C, Sato A, Mayer B, Perelson AS, deCamp A, Priddy FH, Wagh K, Giorgi EE, Yates NL, Arduino RC, DeJesus E, Tomaras GD, Seaman MS, Korber B, Barouch DH. Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial. Nat Med. 2021 Oct;27(10):1718-1724. doi: 10.1038/s41591-021-01509-0. Epub 2021 Oct 7.

Helpful Links

• International AIDS Vaccine Initiative

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ACTUAL): July 8, 2019
• Study Completion (ACTUAL): July 8, 2019

Study Registration Dates

• First Submitted: October 18, 2016
• First Submitted That Met QC Criteria: November 7, 2016
• First Posted (ESTIMATE): November 9, 2016

Study Record Updates

• Last Update Posted (ACTUAL): September 17, 2019
• Last Update Submitted That Met QC Criteria: September 13, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: IAVI T001