Safety and Pharmacokinetics of the Combination Broadly Neutralizing Antibodies, 3BNC117-LS-J and 10-1074-LS-J, in Healthy American and African Adults

NCT04173819 | Completed Phase 1 FDA Drug

• 1 other identifier: IAVI C100
• Study Type: interventional
• Target: 225
• Locations: 5 countries
• Sites: 9

Brief Summary

This is a Phase 1/2 study to evaluate the safety, tolerability, and pharmacokinetics of two broadly neutralizing monoclonal human antibodies (bNAbs), 3BNC117-LS-J, which targets the CD4 binding site on HIV-1 envelope protein, and 10-1074-LS-J which targets the V3 loop of HIV-1 envelope protein. The hypothesis is that the two antibodies will be safe for healthy HIV-1 uninfected adults when co-administered subcutaneously or intravenously and, after subcutaneous administration in the optimal ratio, each antibody will maintain serum levels \>10 µg/ml for at least 3 months in HIV-uninfected participants.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (4)

• 1. Proportion of participants with solicited and treatment-related unsolicited adverse events and their duration.

  92 Weeks

• Proportion of participants with serious adverse events (SAEs) throughout the study period that are considered related to investigational product and their duration.

  92 Weeks

• Serum concentration of each antibody in each group at multiple timepoints along with participant characteristics (e.g. sex, weight, and BMI)

  92 Weeks

• The ratio of 3BNC117-LS-J to 10-1074-LS-J that, when injected SC, will maintain similar levels of each bNAb at steady state.

  92 Weeks

Secondary Outcomes (2)

• Serum concentration of anti-3BNC117-LS-J antibodies in each group at multiple timepoints.

  92 Weeks

• Serum concentration of anti-10-1074-LS-J antibodies in each group at multiple timepoints.

  92 Weeks

Study Arms (10)

Group 1

EXPERIMENTAL

Single Agent, abdominal subcutaneous injection, 10:2 ratio for Ab:placebo

Biological: 3BNC117-LS-J; Biological: Placebo

Group 2

EXPERIMENTAL

Single agent, abdominal subcutaneous injection 10:2 ratio for Ab:placebo

Biological: 10-1074-LS-J; Biological: Placebo

Group 3

EXPERIMENTAL

Single agent intravenous injection 10:2 ratio for Ab:placebo

Biological: 3BNC117-LS-J; Biological: Placebo

Group 4

EXPERIMENTAL

Single agent intravenous injection 10:2 ratio for Ab:placebo

Biological: 10-1074-LS-J; Biological: Placebo

Group 5

EXPERIMENTAL

Combined agent intravenous injection 10:2 ratio for Ab:placebo

Biological: Combination 3BNC117-LS-J and 10-1074-LS-J; Biological: Placebo

Group 6

EXPERIMENTAL

Subcutaneous injection combined ratio 1 with loading dose 30:3 ratio of Ab:Placebo

Biological: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 1; Biological: Placebo

Group 7

EXPERIMENTAL

Subcutaneous injection in abdomen combined ratio 2 with loading dose 30:3 ratio of Ab:Placebo

Biological: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 2; Biological: Placebo

Group 8

EXPERIMENTAL

Subcutaneous injection in abdomen combined ratio 3 with loading dose 30:3 ratio of Ab:Placebo

Biological: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 3; Biological: Placebo

Group 9

EXPERIMENTAL

Subcutaneous injection in abdomen combined ratio 2 without loading dose 30:3 ratio of Ab:Placebo

Biological: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 2; Biological: Placebo

Group 10

EXPERIMENTAL

Subcutaneous injection in arm combined ratio 2 without loading dose 30:3 ratio of Ab:Placebo

Biological: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 2; Biological: Placebo

Interventions

3BNC117-LS-J BIOLOGICAL

300mg

Group 1; Group 3

10-1074-LS-J BIOLOGICAL

300mg

Group 2; Group 4

Combination 3BNC117-LS-J and 10-1074-LS-J BIOLOGICAL

30mg/kg of each

Group 5

Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 1 BIOLOGICAL

Total \~300 mg (\< 2.5 ml) combined of 3BNC117-LS-J and 101074-LS-J - Dosage ratios chosen will be those considered worthy of further investigation based on the safety and preliminary PK observed in groups 1-2

Group 6

Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 2 BIOLOGICAL

Total \~300 mg (\< 2.5 ml) combined of 3BNC117-LS-J and 101074-LS-J - Dosage ratios chosen will be those considered worthy of further investigation based on the safety and preliminary PK observed in groups 1-2

Group 10; Group 7; Group 9

Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 3 BIOLOGICAL

Total \~300 mg (\< 2.5 ml) combined of 3BNC117-LS-J and 101074-LS-J - Dosage ratios chosen will be those considered worthy of further investigation based on the safety and preliminary PK observed in groups 1-2

Group 8

Placebo BIOLOGICAL

0.9% Saline

Group 3; Group 4; Group 5

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female individuals, as assessed by a medical history, physical exam, and laboratory tests
• At least 18 years of age on the day of screening and have not reached their 46th birthday on the day of the first administration
• Willing to undergo HIV testing, risk reduction counseling and receive HIV test results; committed to maintaining low-risk behavior for the trial duration
• Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study
• All male and female participants of reproductive potential who are engaging in sexual activity that could lead to pregnancy must commit to use an effective method of contraception from enrollment until 9 months after the last administration
• Willing to forgo donations of blood, or any other tissues during the study following confirmation of study eligibility and, for those who test HIV-positive due to antibody-induced seropositivity, until the anti-HIV antibody titers become undetectable on HIV tests used in the community

You may not qualify if:

• Confirmed HIV infection
• Reported risk for HIV infection within 6 months prior to investigational product administration, as defined by: Unprotected sexual intercourse with a known HIV-infected person, a partner known to be at high risk for HIV infection and/or a casual partner (i.e. no continuing established relationship), engaged in sex work, frequent excessive daily alcohol use or frequent binge drinking or any other use of illicit drugs, history of newly-acquired syphilis, gonorrhea, non-gonococcal urethritis, HSV-2, chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B or hepatitis C, three or more sexual partners
• Any clinically significant acute or chronic medical condition that is considered progressive or in the opinion of the investigator makes the participant unsuitable for participation in the study
• Infectious disease diagnosis: Hepatitis B infection as measured by HbsAg and/or PCR, Hepatitis C infection (US: HCV RNA positive, or interferon-alpha treatment for hepatitis C infection in the past year, or interferon-alpha-free treatment for hepatitis C infection completed in the past 6 months; Africa: HCV Ab positive and/or PCR positive), active syphilis (positive RPR confirmed by TPHA)
• Receipt of blood transfusion or blood-derived products within the previous 3 months
• Psychiatric condition that compromises safety of the participant and precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years
• Body mass index (BMI) \>40
• Active tuberculosis

Sponsors & Collaborators

• International AIDS Vaccine Initiative: lead
• Fred Hutchinson Cancer Center: collaborator
• Rockefeller University: collaborator
• Brigham and Women's Hospital: collaborator

Study Sites (9)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

The Rockefeller University

New York, New York, 10065, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Partners in Health Research and Development

Thika, Kiambu County, Kenya

Location

Kenya AIDS Vaccine Initiative - Institute of Clinical Research

Nairobi, Kenya

Location

Center for Family Health Research

Kigali, Rwanda

Location

Wits Reproductive Health and HIV Institute

Johannesburg, South Africa

Location

Uganda Virus Research Institute

Entebbe, Uganda

Location

Infectious Diseases Institute Kasangati

Kampala, Uganda

Location

Related Links

• Related Info

Study Officials

• Marina Caskey, MD

  Rockefeller University

  STUDY CHAIR

Study Design

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

Model Details: The study is a randomized, double-blind, placebo-controlled Phase 1/2 study intended to evaluate the safety and pharmacokinetics of 10-1074-LS-J and 3BNC117-LS-J, alone or in combination, in healthy HIV-uninfected individuals.

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: November 22, 2019
• Study Start: January 25, 2019
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

UG (2); KE (2); US (3); RW (1); ZA (1)