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

• 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: Rockefeller University
• Information provided by (Responsible Party): Rockefeller University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV-1 Infection	Drug: 3BNC117; Other: ART Interruption	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel 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
• Actual Study Start Date: March 11, 2015
• Actual Primary Completion Date: March 25, 2017
• Actual Study Completion Date: March 25, 2017

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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.

Secondary Outcome Measures :

1. 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older 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

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

  Study Documents (Full-Text)

Documents provided by Rockefeller University:

Study Protocol  [PDF] September 21, 2015

Statistical Analysis Plan  [PDF] September 21, 2015

Informed Consent Form  [PDF] September 21, 2015

More Information

• Responsible Party: Rockefeller University
• ClinicalTrials.gov Identifier: NCT02446847
• Other Study ID Numbers: MCA-0867
• First Posted: May 18, 2015
• Results First Posted: July 23, 2020
• Last Update Posted: July 23, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rockefeller University:

HIV; 3BNC117; Broadly neutralizing antibody