3BNC117 and 10-1074 in HIV-infected Individuals

• Status: Completed
• Trial end date: 2018-08-15
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase 1b clinical trial to evaluate the safety, pharmacokinetics and the antiretroviral effects of the combination of two anti-human immunodeficiency virus (HIV) broadly neutralizing antibodies, 3BNC117 and 10-1074, administered intravenously in HIV-infected individuals. This study is intended to support the development of the combination of 3BNC117 and 10-1074 mAbs for use in the treatment of HIV-1 infection.

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

Details

• Lead Sponsor: Rockefeller University
• Collaborator: University Hospital of Cologne
• Treatments: Antibodies; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Immunoglobulins

Criteria

Inclusion Criteria:

All groups:

• Age 18 to 65.

• HIV-1 infection confirmed by two independent laboratory assays.

• If sexually active male or female, and participating in sexual activity that could lead to pregnancy, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting intrauterine device (IUD), hormone-based contraceptive with condom) for the study duration.

Groups 1A and 1B:

• HIV-infected volunteers on ART with HIV-1 plasma RNA levels < 20 copies/ml.

• Current CD4 cell count > 300 cells/μl.

Groups 1C and 3:

• HIV-infected volunteers off ART with detectable HIV-1 plasma RNA levels < 100,000 copies/ml by standard assays.

• Current CD4 cell count > 300 cells/μl.

Group 2:

• On antiretroviral therapy for a minimum of 24 months, with plasma HIV-1 RNA levels of < 50 copies/ml for at least 18 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. CD4 cell count nadir > 200 cells/μl.

• If on an NNRTI-based regimen willing to switch to a dolutegravir-based regimen for 4 weeks prior to discontinuing ART.

Exclusion Criteria:

• Have a history of AIDS-defining illness within 3 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.

• Any clinically significant acute or chronic medical condition (such as autoimmune diseases or coronary artery disease), 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 or known resistance to dolutegravir in participants on non-nucleoside reverse-transcriptase inhibitors (NNRTI), who would switch regimen prior to ATI (Group 2).

• Laboratory abnormalities in the parameters listed below:

• Absolute neutrophil count ≤ 1,000 cells/l

• Hemoglobin ≤ 10 gm/dL

• Platelet count ≤ 100,000 cells/l

• Alanine Aminotransferase (AST) ≥ 1.5 x ULN

• Aspartate Aminotransferase (AST) ≥ 1.5 x ULN

• Alkaline phosphatase ≥ 1.5 x ULN

• Total bilirubin > 1.0 ULN

• eGFR < 60 mL/min/1.73m2

• Pregnancy or lactation;

• Any vaccination within 14 days prior to 3BNC117 and 10-1074 administration;

• Subjects with known hypersensitivity to any constituent of the investigational products;

• Receipt of any therapeutic HIV vaccine or 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.