3BNC117 and 10-1074 in HIV Uninfected Adults

NCT02824536 | Completed Phase 1 DMC

• 1 other identifier: YCO-0899
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Human Immunodeficiency Virus

Keywords

3BNC117; 10-1074; Broadly neutralizing antibody; HIV Prevention

Outcome Measures

Primary Outcomes (1)

• The number of participants who experience adverse events within 1 week after the combination of 3BNC117 and 10-1074 infusion in all study groups.

  Adverse events include signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity adverse events.

  1 week following each combination of 3BNC117 and 10-1074 infusion

Secondary Outcomes (3)

• Number of participants with induced anti-3BNC117 and anti-10-1074 antibodies

  8 weeks following each combination of 3BNC117 and 10-1074 infusion

• Level of induced anti-3BNC117 and anti-10-1074 antibodies

  8 weeks following each combination of 3BNC117 and 10-1074 infusion

• The number of participants who experience adverse events that occur during study follow up after 3BNC117 and 10-1074 infusions in all study groups.

  24-40 weeks

Other Outcomes (6)

• Neutralization activity of serum from study participants against a panel of viruses as measured by the TZM.bl neutralization assay.

  24-40 weeks

• Elimination half-life (t1/2) of 3BNC117 and 10-1074

  24-40 weeks

• Clearance (CL/F) of 3BNC117 and 10-1074

  24-40 weeks

Study Arms (3)

Group 1

EXPERIMENTAL

Participants will be randomized in a 3:1 ratio to receive one intravenous infusion of 3BNC117 and one intravenous infusion of 10-1074, each dosed at 10 mg/kg OR placebo (sterile saline), on day 0.

Drug: 3BNC117; Drug: 10-1074; Drug: Placebo

Group 2

EXPERIMENTAL

Participants will be randomized in a 3:1 ratio to receive three intravenous infusions of 3BNC117 and three intravenous infusions of 10-1074, each dosed at 3 mg/kg OR placebo (sterile saline), on day 0, week 8, and week 16.

Drug: 3BNC117; Drug: 10-1074; Drug: Placebo

Group 3

EXPERIMENTAL

Participants will be randomized in a 3:1 ratio to receive three intravenous infusions of 3BNC117 and three intravenous infusions of 10-1074, each dosed at 10 mg/kg OR placebo (sterile saline), on day 0, week 8, and week 16.

Drug: 3BNC117; Drug: 10-1074; Drug: Placebo

Interventions

3BNC117 DRUG

Intravenous Infusion of 3BNC117

Also known as: Monoclonal Antibody 3BNC117

Group 1; Group 2; Group 3

10-1074 DRUG

Intravenous Infusion of 10-1074

Also known as: Monoclonal Antibody 10-1074

Group 1; Group 2; Group 3

Placebo DRUG

Intravenous Infusion of Sterile Saline (NaCl 0.9%)

Also known as: Sterile Saline (NaCl 0.9%)

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females, age 18 to 65.
• Amenable to HIV risk reduction counseling and agrees to maintain behavior consistent with low risk of HIV exposure.
• If sexually active male or female, and participating in sexual activity that could lead to pregnancy, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) for the duration of the study.

You may not qualify if:

• Confirmed HIV-1 or HIV-2 infection.
• History of immunodeficiency or autoimmune disease; use of systemic corticosteroids, immunosuppressive anti-cancer, 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) that in the opinion of the investigator would preclude participation.
• Within the 12 months prior to enrollment, the participant has a history of sexually transmitted infection.
• Chronic Hepatitis B or Hepatitis C infection.
• Laboratory abnormalities in the parameters listed:
• Absolute neutrophil count ≤ 2,000;
• Hemoglobin ≤ 12 gm/dL if female; ≤ 13.5 gm/dL if male;
• Platelet count ≤ 125,000;
• Alanine Aminotransferase (ALT) ≥ 1.25 x ULN; Aspartate Aminotransferase (AST) ≥ 1.25 x ULN;
• Alkaline phosphatase ≥ 1.5 x ULN
• Total bilirubin \> 1.0 x ULN;
• Creatinine ≥1.1 x ULN;
• Pregnancy or lactation.
• Any vaccination within 14 days prior to infusion

Sponsors & Collaborators

• Rockefeller University: lead

Study Sites (1)

The Rockefeller University

New York, New York, 10065, United States

Location

Related Publications (2)

• Valente PK, Wu Y, Cohen YZ, Caskey M, Meyers K. Behavioral and social science research to support development of educational materials for clinical trials of broadly neutralizing antibodies for HIV treatment and prevention. Clin Trials. 2021 Feb;18(1):17-27. doi: 10.1177/1740774520948042. Epub 2020 Aug 24.

  PMID: 32838558 DERIVED

• Cohen YZ, Butler AL, Millard K, Witmer-Pack M, Levin R, Unson-O'Brien C, Patel R, Shimeliovich I, Lorenzi JCC, Horowitz J, Walsh SR, Lin S, Weiner JA, Tse A, Sato A, Bennett C, Mayer B, Seaton KE, Yates NL, Baden LR, deCamp AC, Ackerman ME, Seaman MS, Tomaras GD, Nussenzweig MC, Caskey M. Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study. PLoS One. 2019 Aug 8;14(8):e0219142. doi: 10.1371/journal.pone.0219142. eCollection 2019.

  PMID: 31393868 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

3BNC117 antibody; Sodium Chloride

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)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Yehuda Cohen, MD

  Rockefeller University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2016
• First Posted: July 6, 2016
• Study Start: June 23, 2016
• Primary Completion: January 9, 2018
• Study Completion: January 9, 2018
• Last Updated: April 17, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)