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

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.
    

Detailed description: 
      The proposed study is a Phase 1b clinical trial to evaluate the safety, pharmacokinetics and
      the antiretroviral effects of the combination of two anti-HIV broadly neutralizing
      antibodies, 3BNC117 and 10-1074, administered intravenously in HIV-infected individuals.

      The study includes 5 study groups. Study participants will be administered one or three
      intravenous infusions of 3BNC117 and 10-1074, each mAb dosed at 10 or 30 mg/kg:

      Single dose groups:

      Group 1A (n=6) - HIV-infected individuals, on antiretroviral therapy (ART) with HIV-1 RNA <
      20 copies/ml will be randomized in a 2:1 ratio to receive one intravenous infusion of 3BNC117
      and one infusion of 10-1074, each dosed at 10 mg/kg (n=4), OR placebo (sterile saline; n=2),
      on day 0.

      Group 1B (n=6) - HIV-infected individuals, on ART with HIV-1 RNA < 20 copies/ml will be
      randomized in a 2:1 ratio to receive one intravenous infusion of 3BNC117 and one infusion
      10-1074, each dosed at 30 mg/kg (n=4), OR placebo (sterile saline; n=2), on day 0.

      Participants and investigators will be blinded to study assignment in groups 1A and 1B.

      Group 1C (n=4) - HIV-infected individuals, off ART will be administered one infusion of
      3BNC117 and one infusion 10-1074, each dosed at 30 mg/kg, on day 0.

      Three doses groups:

      Group 2 (n=15) - HIV-infected individuals, on ART who will be administered three infusions of
      3BNC117 and three infusions of 10-1074, each dosed at 30 mg/kg, on days 0, 21 (week 3) and 42
      (week 6). Participants enrolled in Group 2 will discontinue their antiretroviral (ART)
      regimen on day 2.

      Group 3 (n=6) - HIV-infected individuals, off ART who will be administered three infusions of
      3BNC117 and three infusions of 10-1074, each dosed at 30 mg/kg on days 0, 14 (week 2) and 28
      (week 4).

      Following 3BNC117 and 10-1074 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 mAb infusion, then bi-monthly or monthly until the end of
      study follow up.

      Serum samples for PK (pharmacokinetic) measurements will be collected before the start of the
      first mAb infusion. Peak PK sampling for 3BNC117 will occur following the completion of the
      3BNC117 infusion and 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 samples for PK
      assessments will be collected at multiple time points during study follow up.

      Samples will also be collected for measurement of HIV-1 plasma RNA levels before 3BNC117 and
      10-1074 infusions (screen, pre-infusion and day 0), at all follow up visits in Groups 1A, 1B
      and 2, and weekly during the ATI period and at later time points in Group 2.

      All participants will be followed for 24 weeks after the last 3BNC117 and 10-1074 infusions.
    

Intervention name(s): 3BNC117; 10-1074; Analytical treatment interruption; Placebo
Intervention type(s): Drug; Drug; Other; Drug
Intervention description(s): Intravenous infusion of 3BNC117; Intravenous infusion of 10-1074; Analytical treatment interruption; Intravenous infusion of placebo (sterile saline)
Other intervention name(s): Monoclonal Antibody; Monoclonal Antibody; ART interruption; Sterile Saline
Intervention MeSH terms: Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Broadly neutralizing antibody; 3BNC117; 10-1074