3BNC117 and 10-1074 in ART-treated Individuals

NCT03526848 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MCA-0965
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Human Immunodeficiency Virus

Keywords

3BNC117; 10-1074; Broadly Neutralizing Antibody

Outcome Measures

Primary Outcomes (6)

• The change in the size of the functional, latent HIV-1 reservoir between baseline and after seven infusions of 3BNC117 and 10-1074

  The size of the functional, latent HIV-1 reservoir is determined by the number of infectious units per 106 resting memory CD4+ T cells (IUPM) using a viral outgrowth assay at baseline and after seven infusions of 3BNC117 and 10-1074

  Day 0 and week 26

• The size of the proviral HIV-1 reservoir

  Size of the proviral HIV-1 reservoir as determined by total HIV-1 DNA and integrated HIV-1 DNA in circulating total CD4+ T cells before and after seven infusions of 3BNC117 and 10-1074.

  48 weeks

• The rate of viral rebound

  Rate of viral rebound (plasma HIV-1 RNA level \> 200 copies/ml in 2 consecutive measurements) or indication to reinitiate ART at 12 weeks after ART interruption (study week 12 in group 1, study week 38 in group 2).

  Week 12 (group 1) and week 38 (group 2)

• Time to return of HIV-1 viremia

  Time to return of HIV-1 viremia (plasma HIV-1 RNA level \> 200 copies/ml in 2 consecutive measurements) after ART interruption.

  48 weeks

• The rate of adverse events (AE) and serious adverse events (SAE).

  The rate of adverse events (AE) and serious adverse events (SAE).

  48 weeks

• The severity of adverse events (AE) and serious adverse events (SAE).

  The severity of adverse events (AE) and serious adverse events (SAE).

  48 weeks

Secondary Outcomes (2)

• The rate of viral rebound at 26 weeks after ART interruption in group 1.

  26 weeks

• Serum levels of 3BNC117 and 10-1074 at the time of viral rebound

  48 weeks

Study Arms (2)

Group 1

EXPERIMENTAL

HIV infected participants on ART will undergo analytical treatment interruption 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).

Drug: 3BNC117; Drug: 10-1074; Other: Analytical treatment interruption

Group 2

EXPERIMENTAL

HIV infected participants on ART 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). Analytical treatment interruption will begin at week 26 until week 38, if viral suppression is maintained (Part B).

Drug: 3BNC117; Drug: 10-1074; Other: Analytical treatment interruption

Interventions

3BNC117 DRUG

Intravenous infusion of 3BNC117

Also known as: Monoclonal antibody

Group 1; Group 2

10-1074 DRUG

Intravenous infusion of 3BNC117

Also known as: Monoclonal antibody

Group 1; Group 2

Analytical treatment interruption OTHER

Analytical treatment interruption

Also known as: ART interruption

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and females, age 18 to 65.
• Confirmed HIV-1 infection.
• On antiretroviral therapy with plasma HIV-1 RNA levels of \< 50 copies/ml for at least 12 months, and \< 20 copies/ml at screening. Note: a single viral load measurement \> 50 but \< 500 copies/ml during this time period is allowed.
• Current CD4+ T cell counts \> 500 cells/μl and CD4+ T cell count nadir of \> 200 cells/μl.
• If on an NNRTI-based regimen, willing to switch to an integrase inhibitor-based regimen for at least 4 weeks prior to discontinuing ART
• If sexually active male or female, participating in sexual activity that could lead to pregnancy and of reproductive potential, agrees to follow the contraception requirements outlined Section 6.12.12 Family Planning Counseling. Participants should also agree to use a male or female condom while off ART to prevent infecting sexual partners.

You may not qualify if:

• Have a history of AIDS-defining illness within 3 years prior to enrollment.
• History of systemic corticosteroids (long term use), immunosuppressive anti-cancer, interleukins, systemic interferons, systemic chemotherapy or other medications considered significant by the trial physician within the last 6 months.
• Any clinically significant acute or chronic medical condition (such as autoimmune diseases), other than HIV infection, that in the opinion of the investigator would preclude participation.
• Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
• History of resistance to 2 or more classes of antiretroviral medication.
• Laboratory abnormalities in the parameters listed below:
• Absolute neutrophil count ≤ 1,000 cells/μl
• Hemoglobin ≤ 10 gm/dL
• Platelet count ≤ 100,000 cells/μl
• Alanine aminotransferase (ALT) ≥ 1.5 x ULN
• Aspartate aminotransferase (AST) ≥ 1.5 x ULN
• Alkaline phosphatase ≥ 1.5 x ULN
• Total bilirubin ≥ 1.5 x ULN
• eGFR \< 60 mL/min/1.73m2
• Prothrombin time (PT) \> 1.2 x upper limit of normal (ULN). (only if LN biopsies are performed)

Sponsors & Collaborators

• Rockefeller University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Ragon Institute of MGH, MIT and Harvard: collaborator
• Montefiore Medical Center: collaborator

Study Sites (2)

Ragon Institute of MGH, MIT, and Harvard

Boston, Massachusetts, 02114, United States

Location

The Rockefeller University

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

3BNC117 antibody; Antibodies, Monoclonal

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Marina Caskey, MD

  The Rockefeller University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2018
• First Posted: May 16, 2018
• Study Start: June 5, 2018
• Primary Completion: September 30, 2021
• Study Completion: February 11, 2022
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)