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

NCT ID: NCT04173819

Last Updated: 2025-05-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

225 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-25

Study Completion Date

2023-09-01

Brief Summary

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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.

Detailed Description

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Conditions

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HIV-1-infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Group 1

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

Group Type EXPERIMENTAL

3BNC117-LS-J

Intervention Type BIOLOGICAL

300mg

Placebo

Intervention Type BIOLOGICAL

Buffer Solution

Group 2

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

Group Type EXPERIMENTAL

10-1074-LS-J

Intervention Type BIOLOGICAL

300mg

Placebo

Intervention Type BIOLOGICAL

Buffer Solution

Group 3

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

Group Type EXPERIMENTAL

3BNC117-LS-J

Intervention Type BIOLOGICAL

300mg

Placebo

Intervention Type BIOLOGICAL

0.9% Saline

Group 4

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

Group Type EXPERIMENTAL

10-1074-LS-J

Intervention Type BIOLOGICAL

300mg

Placebo

Intervention Type BIOLOGICAL

0.9% Saline

Group 5

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

Group Type EXPERIMENTAL

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

Intervention Type BIOLOGICAL

30mg/kg of each

Placebo

Intervention Type BIOLOGICAL

0.9% Saline

Group 6

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

Group Type EXPERIMENTAL

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

Intervention Type 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

Placebo

Intervention Type BIOLOGICAL

Buffer Solution

Group 7

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

Group Type EXPERIMENTAL

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

Intervention Type 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

Placebo

Intervention Type BIOLOGICAL

Buffer Solution

Group 8

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

Group Type EXPERIMENTAL

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

Intervention Type 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

Placebo

Intervention Type BIOLOGICAL

Buffer Solution

Group 9

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

Group Type EXPERIMENTAL

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

Intervention Type 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

Placebo

Intervention Type BIOLOGICAL

Buffer Solution

Group 10

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

Group Type EXPERIMENTAL

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

Intervention Type 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

Placebo

Intervention Type BIOLOGICAL

Buffer Solution

Interventions

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3BNC117-LS-J

300mg

Intervention Type BIOLOGICAL

10-1074-LS-J

300mg

Intervention Type BIOLOGICAL

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

30mg/kg of each

Intervention Type BIOLOGICAL

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

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

Intervention Type BIOLOGICAL

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

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

Intervention Type BIOLOGICAL

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

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

Intervention Type BIOLOGICAL

Placebo

0.9% Saline

Intervention Type BIOLOGICAL

Placebo

Buffer Solution

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Participation in another clinical trial of an investigational product currently, within the previous 3 months or expected participation during this study (Concurrent participation in an observational trial not requiring blood or tissue sample collection is not an exclusion)
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Fred Hutchinson Cancer Center

OTHER

Sponsor Role collaborator

Rockefeller University

OTHER

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role collaborator

International AIDS Vaccine Initiative

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marina Caskey, MD

Role: STUDY_CHAIR

Rockefeller University

Locations

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Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

The Rockefeller University

New York, New York, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Partners in Health Research and Development

Thika, Kiambu County, Kenya

Site Status

Kenya AIDS Vaccine Initiative - Institute of Clinical Research

Nairobi, , Kenya

Site Status

Center for Family Health Research

Kigali, , Rwanda

Site Status

Wits Reproductive Health and HIV Institute

Johannesburg, , South Africa

Site Status

Uganda Virus Research Institute

Entebbe, , Uganda

Site Status

Infectious Diseases Institute Kasangati

Kampala, , Uganda

Site Status

Countries

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United States Kenya Rwanda South Africa Uganda

Related Links

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http://iavi.org

Related Info

Other Identifiers

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IAVI C100

Identifier Type: -

Identifier Source: org_study_id

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