3BNC117 and 10-1074 in ART-treated Individuals
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, open label, randomized study to evaluate the safety and
      antiretroviral activity of seven infusions of 3BNC117 and 10-1074, administered intravenously
      at 30 mg/kg dose level, in human immunodeficiency virus (HIV)-infected individuals on
      combination antiretroviral therapy (ART) and during an analytical interruption of ART.
    

Detailed description: 
      The proposed study is an open label study of the safety and antiretroviral activity of
      3BNC117 and 10-1074 in HIV-infected individuals with well-controlled HIV infection on
      combination antiretroviral therapy (ART). 3BNC117 and 10-1074 are two broadly neutralizing
      antibodies (bNAbs) that target different sites on HIV-1 gp120. Our hypothesis is that the
      administration of repeated infusions of 3BNC117 and 10-1074 in the absence of ART will be
      safe and well tolerated, will maintain viral suppression in HIV-infected individuals during
      analytical treatment interruption (ATI) and will interfere with the maintenance of the HIV-1
      reservoir.

      Forty eligible participants will be randomized to either Group 1 or Group 2 in a 3:1 ratio:

      Group 1 (n=30): participants will discontinue ART 2 days after the first infusion of 3BNC117
      and 10-1074, and will receive 6 additional infusions of both antibodies at weeks 2, 4, 8, 12,
      16 and 20 (Part A). Participants will remain off ART until week 38, if viral suppression is
      maintained (Part B).

      Group 2 (n=10): participants will remain on ART and will be administered seven infusions of
      3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16 and 20 (Part A). ART will be discontinued at
      week 26 until week 38, if viral suppression is maintained (Part B).

      After screening, participants will remain on ART and undergo leukapheresis, and will have the
      option to undergo LN biopsies 2-4 weeks prior to first 3BNC117 and 10-1074 infusions.

      Participants enrolled in group 1 will discontinue their ART 2 days after the first 3BNC117
      and 10-1074 infusions. Participants enrolled in group 2 will discontinue their ART at week
      26. If the participant's ART regimen includes an NNRTI, the NNRTI will be switched to an
      integrase inhibitor-based regimen, 4 weeks prior discontinuing all antiretroviral drugs.

      During the ATI periods of the study, ART will be resumed if there is a > 30% decline in CD4+
      T cell count or CD4+ T cell count decreases to < 350 cells/μl from baseline (day 0) and these
      changes are confirmed during next visit. ART will also be re-initiated if the participant
      develops symptoms of severe acute retroviral syndrome or becomes pregnant. In addition, ART
      will be resumed according the following virologic parameters:

      Part A (wk 0 - wk 26), ART will be resumed if group 1 participants have 2 consecutive plasma
      HIV-1 RNA levels > 200 copies/ml.

      Part B (wk 26 - wk 38), ART will be resumed if group 1 or group 2 participants have sustained
      (> 4 weeks) HIV-1 RNA levels > 1,000 copies/ml.

      Part C (wk 38 - wk 48), group 1 and group 2 participants who have not met criteria to
      reinitiate ART will be offered to continue off ART with close monitoring. In Part C, ART will
      be resumed if the participant has 2 consecutive plasma HIV-1 RNA levels > 1,000 copies/ml.

      All participants will be followed for a total of 48 weeks from enrollment (day 0).
      Participants will be invited to return for a large blood draw after they reach at least 24
      weeks of viral suppression after ART is re-initiated, if this occurs after the active study
      follow up period.

      Safety assessments will be performed at multiple time points following 3BNC117 and 10-1074
      infusions. The effects of 3BNC117 and 10-1074 infusions on the HIV-1 reservoir of
      ART-suppressed HIV-infected individuals will be evaluated by several assays. These
      evaluations will occur at baseline (day 0) and at week 26.
    

Intervention name(s): 3BNC117; 10-1074; Analytical treatment interruption
Intervention type(s): Drug; Drug; Other
Intervention description(s): Intravenous infusion of 3BNC117; Intravenous infusion of 3BNC117; Analytical treatment interruption
Other intervention name(s): Monoclonal antibody; Monoclonal antibody; ART interruption
Intervention MeSH terms: Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: 3BNC117; 10-1074; Broadly Neutralizing Antibody