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

March 9, 2023 updated by: International AIDS Vaccine Initiative
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.

Study Overview

Study Type

Interventional

Enrollment (Anticipated)

225

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Nairobi, Kenya
        • Kenya AIDS Vaccine Initiative - Institute of Clinical Research
    • Kiambu
      • Thika, Kiambu, Kenya
        • Partners in Health Research and Development
      • Kigali, Rwanda
        • Center for Family Health Research
      • Johannesburg, South Africa
        • Wits Reproductive Health and HIV Institute
      • Entebbe, Uganda
        • Uganda Virus Research Institute
      • Kampala, Uganda
        • Infectious Diseases Institute Kasangati
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
    • New York
      • New York, New York, United States, 10065
        • The Rockefeller University
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1
Single Agent, abdominal subcutaneous injection, 10:2 ratio for Ab:placebo
300mg
0.9% Saline
Buffer Solution
Experimental: Group 2
Single agent, abdominal subcutaneous injection 10:2 ratio for Ab:placebo
0.9% Saline
Buffer Solution
300mg
Experimental: Group 3
Single agent intravenous injection 10:2 ratio for Ab:placebo
300mg
0.9% Saline
Buffer Solution
Experimental: Group 4
Single agent intravenous injection 10:2 ratio for Ab:placebo
0.9% Saline
Buffer Solution
300mg
Experimental: Group 5
Combined agent intravenous injection 10:2 ratio for Ab:placebo
0.9% Saline
Buffer Solution
30mg/kg of each
Experimental: Group 6
Subcutaneous injection combined ratio 1 with loading dose 30:3 ratio of Ab:Placebo
0.9% Saline
Buffer Solution
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
Experimental: Group 7
Subcutaneous injection in abdomen combined ratio 2 with loading dose 30:3 ratio of Ab:Placebo
0.9% Saline
Buffer Solution
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
Experimental: Group 8
Subcutaneous injection in abdomen combined ratio 3 with loading dose 30:3 ratio of Ab:Placebo
0.9% Saline
Buffer Solution
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
Experimental: Group 9
Subcutaneous injection in abdomen combined ratio 2 without loading dose 30:3 ratio of Ab:Placebo
0.9% Saline
Buffer Solution
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
Experimental: Group 10
Subcutaneous injection in arm combined ratio 2 without loading dose 30:3 ratio of Ab:Placebo
0.9% Saline
Buffer Solution
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
1. Proportion of participants with solicited and treatment-related unsolicited adverse events and their duration.
Time Frame: 92 Weeks
92 Weeks
Proportion of participants with serious adverse events (SAEs) throughout the study period that are considered related to investigational product and their duration.
Time Frame: 92 Weeks
92 Weeks
Serum concentration of each antibody in each group at multiple timepoints along with participant characteristics (e.g. sex, weight, and BMI)
Time Frame: 92 Weeks
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.
Time Frame: 92 Weeks
92 Weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Serum concentration of anti-3BNC117-LS-J antibodies in each group at multiple timepoints.
Time Frame: 92 Weeks
92 Weeks
Serum concentration of anti-10-1074-LS-J antibodies in each group at multiple timepoints.
Time Frame: 92 Weeks
92 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Marina Caskey, MD, Rockefeller University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 25, 2019

Primary Completion (Anticipated)

September 1, 2023

Study Completion (Anticipated)

September 1, 2023

Study Registration Dates

First Submitted

November 13, 2019

First Submitted That Met QC Criteria

November 20, 2019

First Posted (Actual)

November 22, 2019

Study Record Updates

Last Update Posted (Estimate)

March 10, 2023

Last Update Submitted That Met QC Criteria

March 9, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • IAVI C100

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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