Back to resultsSafety, PK and Antiviral Activity of PGT121 Monoclonal Antibody in HIV-uninfected and HIV-infected Adults
Primary Purpose
HIV Infection
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PGT121 3mg/kg IV
PGT121 10mg/kg IV
PGT121 30mg/kg IV
PGT121 3mg/kg SC
Placebo (0.9% Sodium Chloride Injection USP (Saline))
Sponsored by
About this trial
This is an interventional prevention trial for HIV Infection
Eligibility 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 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
Sites / Locations
- Beth Israel Deaconess Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Group 1A
Group 1B
Group 1C
Group 2A
Group 2B
Group 2C
Group 3A
Group 3B
Arm 1D
Arm Description
HIV-uninfected participants
HIV-uninfected participants
HIV-uninfected participants
HIV-infected on ART, (<50 cp/ml)
HIV-infected on ART, (<50 cp/ml)
HIV-infected on ART, (<50 cp/ml)
HIV-Infected off ART (VL 2x10^3 - 1x10^5 cp/ml)
HIV-Infected off ART (VL 1x10^2 - 2x10^3 cp/ml)
HIV-uninfected participants
Outcomes
Primary Outcome Measures
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.
Pharmacokinetics: elimination half-life (t1/2)
Pharmacokinetics: elimination half-life (t1/2)
Pharmacokinetics: Clearance (CL/F)
Pharmacokinetics: Clearance (CL/F)
Pharmacokinetics: Volume of distribution (Vz/F)
Pharmacokinetics: Volume of distribution (Vz/F)
Pharmacokinetics: Area under the concentration decay curve (AUC)
Pharmacokinetics: Area under the concentration decay curve (AUC)
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
Antiviral Activity
Change in plasma HIV-1 RNA levels from baseline (mean of pre-entry and entry values)
Secondary Outcome Measures
Full Information
NCT ID
NCT02960581
First Posted
October 18, 2016
Last Updated
September 13, 2019
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
1. Study Identification
Unique Protocol Identification Number
NCT02960581
Brief Title
Safety, PK and Antiviral Activity of PGT121 Monoclonal Antibody in HIV-uninfected and HIV-infected Adults
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 Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
November 2016 (Actual)
Primary Completion Date
July 8, 2019 (Actual)
Study Completion Date
July 8, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the 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
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1A
Arm Type
Experimental
Arm Description
HIV-uninfected participants
Arm Title
Group 1B
Arm Type
Experimental
Arm Description
HIV-uninfected participants
Arm Title
Group 1C
Arm Type
Experimental
Arm Description
HIV-uninfected participants
Arm Title
Group 2A
Arm Type
Experimental
Arm Description
HIV-infected on ART, (<50 cp/ml)
Arm Title
Group 2B
Arm Type
Experimental
Arm Description
HIV-infected on ART, (<50 cp/ml)
Arm Title
Group 2C
Arm Type
Experimental
Arm Description
HIV-infected on ART, (<50 cp/ml)
Arm Title
Group 3A
Arm Type
Experimental
Arm Description
HIV-Infected off ART (VL 2x10^3 - 1x10^5 cp/ml)
Arm Title
Group 3B
Arm Type
Experimental
Arm Description
HIV-Infected off ART (VL 1x10^2 - 2x10^3 cp/ml)
Arm Title
Arm 1D
Arm Type
Experimental
Arm Description
HIV-uninfected participants
Intervention Type
Biological
Intervention Name(s)
PGT121 3mg/kg IV
Intervention Description
3mg/kg administered by IV Infusion
Intervention Type
Biological
Intervention Name(s)
PGT121 10mg/kg IV
Intervention Description
10mg/kg administered by IV infusion
Intervention Type
Biological
Intervention Name(s)
PGT121 30mg/kg IV
Intervention Description
30mg/kg administered by IV infusion
Intervention Type
Biological
Intervention Name(s)
PGT121 3mg/kg SC
Intervention Description
3mg/kg administered by SC injection
Placebo: None
Intervention Type
Biological
Intervention Name(s)
Placebo (0.9% Sodium Chloride Injection USP (Saline))
Primary Outcome Measure Information:
Title
Proportion of participants with PGT121 mAb reactogenicity, related AEs and SAEs
Description
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.
Time Frame
6 Months post infusion
Title
Pharmacokinetics: elimination half-life (t1/2)
Description
Pharmacokinetics: elimination half-life (t1/2)
Time Frame
6 Months post infusion
Title
Pharmacokinetics: Clearance (CL/F)
Description
Pharmacokinetics: Clearance (CL/F)
Time Frame
6 Months post infusion
Title
Pharmacokinetics: Volume of distribution (Vz/F)
Description
Pharmacokinetics: Volume of distribution (Vz/F)
Time Frame
6 months post infusion
Title
Pharmacokinetics: Area under the concentration decay curve (AUC)
Description
Pharmacokinetics: Area under the concentration decay curve (AUC)
Time Frame
6 months post infusion
Title
Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure
Description
Pharmacokinetics: Impact of viral load and/or ART on PGT121 disposition, volume of distribution, total exposure
Time Frame
6 months post infusion
Title
Antiviral Activity
Description
Change in plasma HIV-1 RNA levels from baseline (mean of pre-entry and entry values)
Time Frame
6 Months post infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathryn Stephenson, MD MPH
Organizational Affiliation
Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Boris Juelg, MD PhD
Organizational Affiliation
Ragon Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
34621054
Citation
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.
Results Reference
derived
Links:
URL
http://iavi.org
Description
International AIDS Vaccine Initiative
Learn more about this trial
Safety, PK and Antiviral Activity of PGT121 Monoclonal Antibody in HIV-uninfected and HIV-infected Adults
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