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3BNC117 and 10-1074 in ART-treated Individuals

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ClinicalTrials.gov Identifier: NCT03526848
Recruitment Status : Recruiting
First Posted : May 16, 2018
Last Update Posted : June 19, 2018
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Ragon Institute of MGH, MIT and Harvard
Montefiore Medical Center
Information provided by (Responsible Party):
Rockefeller University

Brief Summary:
The proposed study is a phase 1, open label, randomized study to evaluate the safety and antiretroviral activity of seven infusions of 3BNC117 and 10-1074, administered intravenously at 30 mg/kg dose level, in human immunodeficiency virus (HIV)-infected individuals on combination antiretroviral therapy (ART) and during an analytical interruption of ART.

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Drug: 3BNC117 Drug: 10-1074 Other: Analytical treatment interruption Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Randomized Study of the Safety and Antiretroviral Activity of 3BNC117 and 10-1074 in HIV-infected Individuals on Combination Antiretroviral Therapy and During Analytical Treatment Interruption.
Actual Study Start Date : June 5, 2018
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Group 1
HIV infected participants on ART will undergo analytical treatment interruption 2 days after the first infusion of 3BNC117 and 10-1074, and will receive 6 additional infusions of both antibodies at weeks 2, 4, 8, 12, 16 and 20 (Part A). Participants will remain off ART until week 38, if viral suppression is maintained (Part B).
Drug: 3BNC117
Intravenous infusion of 3BNC117
Other Name: Monoclonal antibody

Drug: 10-1074
Intravenous infusion of 3BNC117
Other Name: Monoclonal antibody

Other: Analytical treatment interruption
Analytical treatment interruption
Other Name: ART interruption

Experimental: Group 2
HIV infected participants on ART will remain on ART and will be administered seven infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16 and 20 (Part A). Analytical treatment interruption will begin at week 26 until week 38, if viral suppression is maintained (Part B).
Drug: 3BNC117
Intravenous infusion of 3BNC117
Other Name: Monoclonal antibody

Drug: 10-1074
Intravenous infusion of 3BNC117
Other Name: Monoclonal antibody

Other: Analytical treatment interruption
Analytical treatment interruption
Other Name: ART interruption




Primary Outcome Measures :
  1. The change in the size of the functional, latent HIV-1 reservoir between baseline and after seven infusions of 3BNC117 and 10-1074 [ Time Frame: Day 0 and week 26 ]
    The size of the functional, latent HIV-1 reservoir is determined by the number of infectious units per 106 resting memory CD4+ T cells (IUPM) using a viral outgrowth assay at baseline and after seven infusions of 3BNC117 and 10-1074

  2. The size of the proviral HIV-1 reservoir [ Time Frame: 48 weeks ]
    Size of the proviral HIV-1 reservoir as determined by total HIV-1 DNA and integrated HIV-1 DNA in circulating total CD4+ T cells before and after seven infusions of 3BNC117 and 10-1074.

  3. The rate of viral rebound [ Time Frame: Week 12 (group 1) and week 38 (group 2) ]
    Rate of viral rebound (plasma HIV-1 RNA level > 200 copies/ml in 2 consecutive measurements) or indication to reinitiate ART at 12 weeks after ART interruption (study week 12 in group 1, study week 38 in group 2).

  4. Time to return of HIV-1 viremia [ Time Frame: 48 weeks ]
    Time to return of HIV-1 viremia (plasma HIV-1 RNA level > 200 copies/ml in 2 consecutive measurements) after ART interruption.

  5. The rate of adverse events (AE) and serious adverse events (SAE). [ Time Frame: 48 weeks ]
    The rate of adverse events (AE) and serious adverse events (SAE).

  6. The severity of adverse events (AE) and serious adverse events (SAE). [ Time Frame: 48 weeks ]
    The severity of adverse events (AE) and serious adverse events (SAE).


Secondary Outcome Measures :
  1. The rate of viral rebound at 26 weeks after ART interruption in group 1. [ Time Frame: 26 weeks ]
    Rate of viral rebound (plasma HIV-1 RNA level > 200 copies/ml in 2 consecutive measurements) at 26 weeks after ART interruption in group 1.

  2. Serum levels of 3BNC117 and 10-1074 at the time of viral rebound [ Time Frame: 48 weeks ]
    Serum levels of 3BNC117 and 10-1074 at the time of viral rebound



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

Inclusion Criteria:

  • Male and females, age 18 to 65.
  • Confirmed HIV-1 infection.
  • On antiretroviral therapy with plasma HIV-1 RNA levels of < 50 copies/ml for at least 12 months, and < 20 copies/ml at screening. Note: a single viral load measurement > 50 but < 500 copies/ml during this time period is allowed.
  • Current CD4+ T cell counts > 500 cells/μl and CD4+ T cell count nadir of > 200 cells/μl.
  • If on an NNRTI-based regimen, willing to switch to an integrase inhibitor-based regimen for at least 4 weeks prior to discontinuing ART
  • If sexually active male or female, participating in sexual activity that could lead to pregnancy and of reproductive potential, agrees to follow the contraception requirements outlined Section 6.12.12 Family Planning Counseling. Participants should also agree to use a male or female condom while off ART to prevent infecting sexual partners.

Exclusion Criteria:

  • Have a history of AIDS-defining illness within 3 years prior to enrollment.
  • History of systemic corticosteroids (long term use), immunosuppressive anti-cancer, interleukins, systemic interferons, systemic chemotherapy or other medications considered significant by the trial physician within the last 6 months.
  • Any clinically significant acute or chronic medical condition (such as autoimmune diseases), other than HIV infection, that in the opinion of the investigator would preclude participation.
  • Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
  • History of resistance to 2 or more classes of antiretroviral medication.
  • Laboratory abnormalities in the parameters listed below:
  • Absolute neutrophil count ≤ 1,000 cells/μl
  • Hemoglobin ≤ 10 gm/dL
  • Platelet count ≤ 100,000 cells/μl
  • Alanine aminotransferase (ALT) ≥ 1.5 x ULN
  • Aspartate aminotransferase (AST) ≥ 1.5 x ULN
  • Alkaline phosphatase ≥ 1.5 x ULN
  • Total bilirubin ≥ 1.5 x ULN
  • eGFR < 60 mL/min/1.73m2
  • Prothrombin time (PT) > 1.2 x upper limit of normal (ULN). (only if LN biopsies are performed)
  • Partial Thromboplastin Time (PTT) > 1.2 x upper limit of normal (ULN) (only if LN biopsies are performed)
  • Pregnancy or lactation
  • Receipt of any therapeutic HIV vaccine or anti-HIV monoclonal antibody therapy in the past.
  • Participants with known hypersensitivity to any constituent of the investigational products.
  • Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.
  • History of intolerance, sensitivity, allergy or anaphylaxis to benzodiazepines or other narcotics to be used during LN biopsy. (only if LN biopsies are performed)
  • Previous adverse reaction or allergy to lidocaine or other amide anesthetics, as well as benzocaine or other ester type anesthetics. (only if LN biopsies are performed)
  • History of underlying medical condition for which antibiotic prophylaxis for invasive procedures is required (only if LN biopsies are performed)
  • Currently taking anticoagulants including but not limited to: heparin (Hep-Lock, Hep-Pak, Hep-Pak CVC, Heparin Lock Flush), warfarin (Coumadin), tinzaparin (Innohep), enoxaparin (Lovenox), danaparoid (Orgaran), dalteparin (Fragmin), clopidogrel (Plavix), dipyridamole (Persantine), fondaparinux (Arixtra), argatroban (Agratroban), and bivalrudin (Angiomax). Prophylactic aspirin and regular NSAID use permitted. (only if LN biopsies are performed)

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): NCT03526848


Contacts
Contact: Recruitment Specialist 800-782-2737 rucares@rockefeller.edu

Locations
United States, New York
The Rockefeller University Recruiting
New York, New York, United States, 10065
Contact: Recruitment Specialist    800-782-2737    rucares@rockefeller.edu   
Principal Investigator: Marina Caskey, MD         
Sub-Investigator: Yehuda Cohen, MD         
Sub-Investigator: Allison Butler, NP         
Sponsors and Collaborators
Rockefeller University
National Institute of Allergy and Infectious Diseases (NIAID)
Ragon Institute of MGH, MIT and Harvard
Montefiore Medical Center
Investigators
Study Chair: Marina Caskey, MD The Rockefeller University

Responsible Party: Rockefeller University
ClinicalTrials.gov Identifier: NCT03526848     History of Changes
Other Study ID Numbers: MCA-0965
1U01AI129825 ( U.S. NIH Grant/Contract )
First Posted: May 16, 2018    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Keywords provided by Rockefeller University:
3BNC117
10-1074
Broadly Neutralizing Antibody

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs