3BNC117 and 10-1074 in ART-treated Individuals

Human Immunodeficiency Virus Clinical Trial

Official title: An Open Label, Randomized Study of the Safety and Antiretroviral Activity of 3BNC117 and 10-1074 in HIV-infected Individuals on Combination Antiretroviral Therapy and During Analytical Treatment Interruption.

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus

• NCT number: NCT03526848
• Study type: Interventional
• Source: Rockefeller University
• Status: Completed
• Phase: Phase 1
• Start date: June 5, 2018
• Completion date: February 11, 2022