3BNC117 and 10-1074 in ART-treated Individuals

• Status: Active, not recruiting
• Trial end date: 2022-04-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rockefeller University
• Collaborators: Montefiore Medical Center; National Institute of Allergy and Infectious Diseases (NIAID); Ragon Institute of MGH, MIT and Harvard
• Treatments: Antibodies; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Immunoglobulins

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)