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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02446847
First Posted: May 18, 2015
Last Update Posted: March 13, 2017
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.
Information provided by (Responsible Party):
Rockefeller University
  Purpose
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.

Condition Intervention Phase
HIV-1 Infection Drug: 3BNC117 Other: ART Interruption Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Rockefeller University:

Primary Outcome Measures:
  • Rate of virologic rebound at 8 weeks after interruption of antiretroviral therapy [ Time Frame: 12 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, in addition to systemic reactogenicity events following four 3BNC117 infusions at 30 mg/kg [ Time Frame: 36 weeks ]
  • 3BNC117 serum levels and anti-drug (3BNC117) antibody responses in serum or plasma at multiple time points following 3BNC117 intravenous administrations. [ Time Frame: 36 weeks ]

Secondary Outcome Measures:
  • The plasma level of 3BNC117 at the time of viral rebound. [ Time Frame: 12 weeks ]

Enrollment: 16
Study Start Date: March 2015
Estimated Study Completion Date: March 2018
Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02446847


Locations
United States, New York
The Rockefeller University
New York, New York, United States, 10065
Sponsors and Collaborators
Rockefeller University
Investigators
Principal Investigator: Marina Caskey, MD The Rockefeller University
  More Information

Responsible Party: Rockefeller University
ClinicalTrials.gov Identifier: NCT02446847     History of Changes
Other Study ID Numbers: MCA-0867
First Submitted: March 17, 2015
First Posted: May 18, 2015
Last Update Posted: March 13, 2017
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Rockefeller University:
HIV
3BNC117
Broadly neutralizing antibody

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs


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