3BNC117 and 10-1074 in HIV Uninfected Adults
Condition: Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase 1 clinical trial to evaluate the safety and pharmacokinetics of the highly
      neutralizing anti-human immunodeficiency virus-1 monoclonal antibodies 3BNC117 and 10-1074,
      when given in combination, in human immunodeficiency virus (HIV)-uninfected individuals. This
      study is intended to support the development of the combination of 3BNC117 and 10-1074 mAbs
      for use as prophylaxis against HIV infection in healthy HIV-uninfected individuals at risk
      for HIV infection.
    

Detailed description: 
      The study will be conducted under a placebo-controlled, double blind, randomized allocation
      of the study products. Study participants in each study group will be randomized to receive
      intravenous infusions of 3BNC117 and 10-1074 or placebo. 3BNC117 and 10-1074 will be
      administered at 2 dose levels (3 mg/kg and 10 mg/kg). These doses were selected based on the
      planned development of subcutaneous formulations for the prophylactic use of these products.
      The study will consist of 3 groups. Enrollment in Group 1 will begin first and participants
      will be enrolled at least one day apart. Eight participants will be enrolled in each group; 6
      will be randomized receive the study drugs and 2 will be randomized to receive placebo.
      Participants in Group 1 will receive a single infusion of each antibody at 10mg/kg at Week 0.
      Enrollment in Group 2 will begin only after Day 28 safety data from all participants in Group
      1, including ophthalmologic exams, are available. Enrollment in Group 3 will begin only after
      the Day 28 safety data from all participants in Group 2 is available. If > 1 grade 3 or
      higher adverse events deemed probably or definitely related to the study drugs occurs in a
      single group, the next group will not be enrolled pending safety monitoring committee (SMC)
      review. Participants in Groups 2 and 3 will receive 3 infusions of each antibody at Weeks 0,
      8, and 16, at a dose of either 3mg/kg or 10mg/kg. The antibodies will be administered
      sequentially via intravenous infusion. Each antibody will be administered over 60 minutes.

      Following product infusions, study participants will return for safety assessments at
      multiple time points. Blood samples will be collected for safety testing at weeks 1, 2, and 4
      following each infusion, then at multiple time points until the end of study follow up.

      Baseline pharmacokinetic (PK) assessments will be performed before the start of the first
      infusion. Peak PK sampling for 3BNC117 will occur following the completion of the 3BNC117
      infusion prior to the start of the 10-1074 infusion. Peak PK sampling for 10-1074 will occur
      following the completion of the 10-1074 infusion. Additional PK assessments will occur at
      multiple time points during study follow up. Study participants will be followed for a total
      of 24 weeks following the final antibody infusion.
    

Intervention name(s): 3BNC117; 10-1074; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Intravenous Infusion of 3BNC117; Intravenous Infusion of 10-1074; Intravenous Infusion of Sterile Saline (NaCl 0.9%)
Other intervention name(s): Monoclonal Antibody 3BNC117; Monoclonal Antibody 10-1074; Sterile Saline (NaCl 0.9%)
Intervention MeSH terms: Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: 3BNC117; 10-1074; Broadly neutralizing antibody; HIV Prevention