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

This study is enrolling participants by invitation only.
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Ragon Institute of MGH, MIT and Harvard
Information provided by (Responsible Party):
International AIDS Vaccine Initiative
ClinicalTrials.gov Identifier:
NCT02960581
First received: October 18, 2016
Last updated: March 6, 2017
Last verified: March 2017
  Purpose
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 Intervention Phase
HIV Infection
Biological: PGT121
Biological: Placebo (0.9% Sodium Chloride Injection USP (Saline))
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by International AIDS Vaccine Initiative:

Primary Outcome Measures:
  • 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.

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

Estimated Enrollment: 63
Study Start Date: November 2016
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


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.
  Eligibility

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02960581

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
Ragon Institute of MGH, MIT and Harvard
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

Additional Information:
Responsible Party: International AIDS Vaccine Initiative
ClinicalTrials.gov Identifier: NCT02960581     History of Changes
Other Study ID Numbers: IAVI T001
Study First Received: October 18, 2016
Last Updated: March 6, 2017

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, Monoclonal
Antibodies
Antiviral Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 25, 2017