Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

3BNC117 Monoclonal Antibody in HIV-infected Subjects During Treatment Interruption

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02446847
Recruitment Status : Completed
First Posted : May 18, 2015
Results First Posted : July 23, 2020
Last Update Posted : July 23, 2020
Sponsor:
Information provided by (Responsible Party):
Rockefeller University

Tracking Information
First Submitted Date  ICMJE March 17, 2015
First Posted Date  ICMJE May 18, 2015
Results First Submitted Date  ICMJE June 3, 2020
Results First Posted Date  ICMJE July 23, 2020
Last Update Posted Date July 23, 2020
Actual Study Start Date  ICMJE March 11, 2015
Actual Primary Completion Date March 25, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 8, 2020)
  • Number of Participants With Virologic Rebound at 8 Weeks After Interruption of Antiretroviral Therapy [ Time Frame: 8 weeks ]
    Virologic rebound is defined as confirmed plasma HIV-1 RNA level > 200 copies/ml in two separate occasions
  • The Rate of Signs, Symptoms and Laboratory Abnormalities After 3BNC117 Infusions [ Time Frame: 36 weeks ]
    The percentage of participants who experienced adverse events (e.g. signs, symptoms and laboratory abnormalities) following 3BNC117 infusions.
Original Primary Outcome Measures  ICMJE
 (submitted: May 13, 2015)
Number of participants with virologic rebound at 12 weeks after interruption of antiretroviral therapy [ Time Frame: 12 weeks ]
Virologic rebound is defined as confirmed plasma HIV-1 RNA level > 200 copies/ml
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2020)
The Plasma Level of 3BNC117 at the Time of Viral Rebound. [ Time Frame: 36 weeks ]
The plasma concentrations of 3BNC117 at the time of viral rebound (i.e. confirmed plasma HIV-1 RNA levels > 200 copies/ml).
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 3BNC117 Monoclonal Antibody in HIV-infected Subjects During Treatment Interruption
Official Title  ICMJE A Phase 2, Open Label Study of the Safety, Antiretroviral Activity and Pharmacokinetics of 3BNC117 During a Short Analytical Treatment Interruption in HIV-infected Subjects
Brief Summary This study evaluates the effects of two infusions of 3BNC117 in preventing or delaying rebound of viral load during a brief treatment interruption of standard ART and its safety during a brief analytical interruption of antiretroviral therapy.
Detailed Description

The proposed study is a Phase II, open label study to evaluate the safety and antiretroviral activity of two and four infusions of 3BNC117 in HIV-infected subjects on combination ART during a brief analytical treatment interruption.

After meeting enrollment criteria sixteen subjects with 3BNC117 sensitive virus (<2μg/ml IC50) will receive two (Group A) or four (Group B) intravenous infusions of 3BNC117, administered at 30 mg/kg.

In both dosing groups, antiretroviral therapy will be discontinued 2 days after the first 3BNC117 infusion (day 2) until week 12. Combination ART will be resumed at week 12. ART will be resumed sooner if plasma HIV-1 RNA level is ≥ 200 copies/ml or if CD4+ count drops < 350 cells/μl and either result is confirmed upon repeat measurement. Participants will be followed weekly until week 12 for safety assessments and for monitoring plasma HIV-1 RNA levels (viral load). CD4+ T cell counts will be monitored every 2 weeks until week 12.

Participants may remain off antiretroviral therapy after week 12, with weekly viral load monitoring, if viral rebound does not occur by week 12. Participants will be followed for a total of 36 weeks.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV-1 Infection
Intervention  ICMJE
  • Drug: 3BNC117
    3BNC117 infusions
    Other Name: 3BNC117 antibody
  • Other: ART Interruption
    Antiretroviral therapy will be discontinued 2 days after the first 3BNC117 infusion (day 2) and resumed at week 12.
    Other Name: Treatment Interruption
Study Arms  ICMJE
  • Experimental: Group A: 3BNC117 IV + ART Interruption
    Two intravenous infusions of 3BNC117 (30 mg/kg) at day 0 and day 21, with interruption of antiretroviral treatment (ART) at day 2.
    Interventions:
    • Drug: 3BNC117
    • Other: ART Interruption
  • Experimental: Group B: 3BNC117 IV + ART interruption
    Four intravenous infusions of 3BNC117 (30 mg/kg) at day 0, day 14, day 28, and day 42 with interruption of antiretroviral treatment (ART) at day 2.
    Interventions:
    • Drug: 3BNC117
    • Other: ART Interruption
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 26, 2015)
16
Original Estimated Enrollment  ICMJE
 (submitted: May 13, 2015)
15
Actual Study Completion Date  ICMJE March 25, 2017
Actual Primary Completion Date March 25, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 18 to 65
  • HIV-1 infection confirmed by ELISA and immunoblot.
  • Plasma HIV-1 RNA < 50 copies/ml for at least 12 months while on combination ART and < 20 copies/ml at the screening visit. [Note: One or two viral blips of < 200 copies/mL prior to enrollment are permitted if preceded and followed by test results showing VL less than or equal to 50 copies/mL on the same ARV regimen.]
  • 3BNC117 sensitivity (IC50 < 2 μg/ml) of subject derived HIV-1 virus isolates. These are isolated under protocol MCA-823 by co-culture of subject PBMCs with HIV-uninfected donor PBMCs followed by in vitro neutralization assays as previously described
  • Current CD4 cell count > 500 cells/μl and no prior CD4 cell count < 200 cells/μl.
  • Willing to interrupt antiretroviral treatment for 12 weeks, or until viral rebound occurs.
  • If sexually active male or female, and participating in sexual activity that could lead to pregnancy using an effective method of contraception throughout the study period. Subjects should also agree to use a male or female condom during the time of pausing their HIV medication.
  • If on an NNRTI-based regimen willing to a switch for 4 weeks to dolutegravir.

Exclusion Criteria:

  • Have a history of AIDS-defining illness within 1 year prior to enrollment
  • History of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months;
  • Chronic hepatitis B or hepatitis C;
  • Patient report, or chart history, of significant coronary artery disease, myocardial infarction, percutaneous coronary intervention with placement of cardiac stents;
  • Patient report, or chart history, of diabetes type 1 or 2 and/or current use of insulin or oral hypoglycemic medications;
  • Uncontrolled hypertension, as defined by a systolic blood pressure > 180 and/or diastolic blood pressure > 120, in the presence or absence of anti-hypertensive medications;
  • Any other clinically significant acute or chronic medical condition, such as autoimmune diseases, that in the opinion of the investigator would preclude participation;
  • Current cigarette use in excess of 1 pack per day;
  • Laboratory abnormalities in the parameters listed below:

    • Absolute neutrophil count ≤1,000
    • Hemoglobin ≤ 10 gm/dL
    • Platelet count ≤125,000
    • ALT ≥ 2.0 x ULN
    • AST ≥ 2.0 x ULN
    • Total bilirubin ≥ 1.5 ULN
    • Creatinine ≥ 1.1 x ULN
    • Coagulation parameters ≥ 1.5 x ULN;
  • Current antiretroviral regimen includes either maraviroc or enfuvirtide;
  • Pregnancy or lactation;
  • Any vaccination within 14 days prior to 3BNC117 administration;
  • Receipt of any monoclonal antibody therapy of any kind in the past;
  • Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.
  • History of resistance to two or more antiretroviral drug classes
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02446847
Other Study ID Numbers  ICMJE MCA-0867
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Rockefeller University
Study Sponsor  ICMJE Rockefeller University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marina Caskey, MD The Rockefeller University
PRS Account Rockefeller University
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP