First-in-human Study of 10-1074-LS Alone and in Combination With 3BNC117-LS
Condition: Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      This first clinical study of 10-1074-LS will evaluate its safety, tolerability and
      pharmacokinetics profile when administered alone or in combination with 3BNC117-LS to HIV
      (human immunodeficiency virus) -infected and HIV-uninfected individuals.
    

Detailed description: 
      The proposed study is a Phase 1, dose escalation cohort study of 10-1074-LS alone or in
      combination with 3BNC117-LS, administered intravenously and subcutaneously in HIV uninfected
      and HIV-1 infected individuals.

      Study participants will be administered a single intravenous infusion of 10-1074-LS at 3, 10
      or 30 mg/kg, single infusions of the combination of 10-1074-LS and 3BNC117-LS, each dosed at
      30 mg/kg, or subcutaneous injections of 10-1074-LS alone or in combination with 3BNC117-LS,
      and three subcutaneous injections of 10-1074-LS in combination with 3BNC117-LS at three dose
      ratios. The first four groups administered subcutaneous injections of the product(s) will be
      randomized, double-blinded, and placebo-controlled to assess potential differences in safety
      and tolerability of the antibody formulation versus the formulation buffer alone. In the dose
      ratio portion of the study, participants will be randomized into one of three groups, but the
      products will be administered in an open-label manner. Groups administered intravenous
      infusions will be enrolled in an open-label manner.

      PART A

      Group 1A (n=8) - HIV-uninfected individuals will be administered one 1 mL (approximately 150
      mg) subcutaneous injection of 10-1074-LS or placebo (formulation buffer), in a 3:1 ratio.

      Group 1B (n=8) - HIV-uninfected individuals will be administered one 2 mL (approximately 300
      mg) subcutaneous injection of 10-1074-LS or placebo (formulation buffer), in a 3:1 ratio.

      Group 2A (n=3) - HIV-uninfected individuals will be administered one intravenous infusion of
      10-1074-LS dosed at 3 mg/kg.

      Group 2B (n=3) - HIV-uninfected individuals will be administered one intravenous infusion of
      10-1074-LS dosed at 10 mg/kg.

      Group 2C (n=3) - HIV-uninfected individuals will be administered one intravenous infusion of
      10-1074-LS dosed at 30 mg/kg.

      Group 3B (n=3) - HIV-infected individuals (on ART) will be administered one intravenous
      infusion of 10-1074-LS dosed at 10 mg/kg.

      Group 3C (n=3) - HIV-infected individuals (on ART) will be administered one intravenous
      infusion of 10-1074-LS dosed at 30 mg/kg.

      PART B

      Part B will begin after the Safety Monitoring Committee (SMC) evaluates available safety data
      from Part A, as detailed below. The SMC will also review available safety data with
      3BNC117-LS administered intravenously collected under protocol YCO-0946 prior to enrollment
      in Part B of this study. The SMC will also review subcutaneous dosing at approximately 150 mg
      (1 mL) and 300 mg (2 mL), collected under IND 131873 when available and prior to enrollment
      in Part B of this study.

      Group 4A (n=8) - HIV-uninfected individuals will be administered one 2 mL (approximately 150
      mg of each mAb) subcutaneous injection of 10-1074-LS admixed with 3BNC117-LS or placebo
      (formulation buffer), in a 3:1 ratio.

      Group 4B (n=8) - HIV-uninfected individuals will be administered two 2 mL (approximately 300
      mg of each mAb) subcutaneous injections of 10-1074-LS admixed with 3BNC117-LS or placebo
      (formulation buffer), in a 3:1 ratio.

      Group 5 (n=5) - HIV-uninfected individuals will be administered one intravenous infusion of
      10-1074-LS and one intravenous infusion of 3BNC117-LS, each dosed at 30 mg/kg.

      Group 6 (n=5) - HIV-infected individuals (on ART) will be administered one intravenous
      infusion of 10-1074-LS and one intravenous infusion of 3BNC117-LS, each dosed at 30 mg/kg.

      Group 7 (n=6) HIV-uninfected individuals will be administered three subcutaneous injections
      of 10-1074-LS (100 mg) admixed with 3BNC117-LS (200 mg) (2 mL).

      Group 8 (n=6) HIV-uninfected individuals will be administered three subcutaneous injections
      of 10-1074-LS (75 mg) admixed with 3BNC117-LS (225 mg) (2 mL).

      Group 9 (n=6) HIV-uninfected individuals will be administered three subcutaneous injections
      of 10-1074-LS (60 mg) admixed with 3BNC117-LS (240 mg) (2 mL).

      Following mAb or placebo administration, study participants will return for safety
      assessments on days 1 and 3, and weeks 1, 2 and 4 following each dose, then bi-monthly or
      monthly until the end of study follow up.

      All participants will be followed for 48 weeks after last mAb or placebo administration.
      Serum samples for PK measurements will be collected before and at the end each mAb or placebo
      administration and at multiple subsequent time points during study follow up.

      Samples will also be collected for measurement of HIV-1 plasma RNA levels before 10-1074-LS
      and 3BNC117-LS infusions and at follow up visits according to protocol.
    

Intervention name(s): 10-1074-LS; 10-1074-LS; 3BNC117-LS; 3BNC117-LS
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Subcutaneous injection of 10-1074-LS; Intravenous infusion of 10-1074-LS; Subcutaneous injection of 3BNC117-LS; Intravenous infusion of 3BNC117-LS
Other intervention name(s): Monoclonal antibody; Monoclonal antibody; Monoclonal antibody; Monoclonal antibody
Intervention MeSH terms: Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: 10-1074-LS; 3BNC117-LS; First in Human; Dose Escalation