3BNC117-LS First-in-Human Phase 1 Study
Condition: Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The proposed study is a phase 1 study of the mAb 3BNC117-LS administered intravenously in HIV
      uninfected individuals and HIV-infected individuals, and subcutaneously in HIV-uninfected
      individuals.The objectives of the study are to evaluate the safety, tolerability and
      pharmacokinetics of a single administration of 3BNC117-LS.
    

Detailed description: 
      The proposed study is a Phase 1, open label, dose escalation cohort study of 3BNC117-LS
      administered intravenously in HIV-uninfected and HIV-1 infected participants.

      This study consists of two parts. In part A, study participants will be enrolled in an open
      label manner to receive a single intravenous infusion of 3BNC117-LS at one of three
      increasing dose levels (3 mg/kg, 10 mg/kg and 30 mg/kg). Participants in Part B will also
      receive a single administration of 3BNC117-LS, however, the product administered in Part B of
      the study derives from a new manufacturing lot. The manufacturing lot used in Part A had
      incomplete glycosylation of the 3BNC117-LS light chain, which has been corrected in the new
      lot. Participants in Part B will receive 3BNC117-LS intravenously at 30 mg/kg in an open
      label manner (HIV-uninfected and HIV-infected) or will be randomized to receive a
      subcutaneous injection of 3BNC117-LS or placebo in a double-blinded fashion (HIV-uninfected
      only).

      Part A has already been enrolled with 21 participants. Part B has a planned enrollment of 22
      participants.

      Part A

        -  Group 1A (n=3-6) - HIV-uninfected individuals will be administered one infusion of
           3BNC117-LS dosed at 3 mg/kg.

        -  Group 1B (n=3-6) - HIV-uninfected individuals will be administered one infusion of
           3BNC117-LS dosed at 10 mg/kg.

        -  Group 1C (n=3-6) - HIV-uninfected individuals will be administered one infusion of
           3BNC117-LS dosed at 30 mg/kg.

        -  Group 2B (n=6) - HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20
           copies/ml or off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000
           copies/ml, will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.

        -  Group 2C (n=6) - HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20
           copies/ml, or off ART for at least 8 weeks with HIV-1 plasma RNA levels < 100,000
           copies/ml, will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.

      Part B

        -  Group 1D (n=3) - HIV-uninfected individuals will be administered one infusion of
           3BNC117-LS dosed at 30 mg/kg.

        -  Group 2D (n=3) - HIV-infected individuals on ART with HIV-1 plasma RNA levels < 20
           copies/ml will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.

        -  Group 1E (n=8) - HIV-uninfected individuals will be administered a single 1 mL
           (approximately 150 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.

        -  Group 1F (n=8) - HIV-uninfected individuals will be administered a single 2 mL
           (approximately 300 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.

      Following 3BNC117-LS infusion, study participants will return for safety assessments at weeks
      1, 2 and 4 following infusion, then bi-monthly or monthly until the end of study follow up.

      Serum samples for PK (pharmacokinetic) measurements will be collected before 3BNC117-LS
      infusion, at the end of the infusion, and at multiple time points during study follow up.

      Samples will also be collected for measurement of HIV-1 plasma RNA levels before 3BNC117-LS
      infusion (screen, pre-infusion and day 0) and at all follow up visits in Groups 2B and 2C.

      All participants will be followed for 48 weeks after 3BNC117-LS administration.
    

Intervention name(s): 3BNC117-LS; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Intravenous infusion of 3BNC117-LS; Placebo
Other intervention name(s): Monoclonal Antibody
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Broadly Neutralizing Antibody; 3BNC117-LS; First in Human; Dose Escalation