- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04173819
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
Status
Active, not recruiting
Conditions
Intervention / Treatment
- Biological: 3BNC117-LS-J
- Biological: Placebo
- Biological: Placebo
- Biological: 10-1074-LS-J
- Biological: Combination 3BNC117-LS-J and 10-1074-LS-J
- Biological: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 1
- Biological: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 2
- Biological: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 3
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
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Nairobi, Kenya
- Kenya AIDS Vaccine Initiative - Institute of Clinical Research
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Kiambu
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Thika, Kiambu, Kenya
- Partners in Health Research and Development
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Kigali, Rwanda
- Center for Family Health Research
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Johannesburg, South Africa
- Wits Reproductive Health and HIV Institute
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Entebbe, Uganda
- Uganda Virus Research Institute
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Kampala, Uganda
- Infectious Diseases Institute Kasangati
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
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New York
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New York, New York, United States, 10065
- The Rockefeller University
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Washington
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Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center
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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 |
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Experimental: Group 1
Single Agent, abdominal subcutaneous injection, 10:2 ratio for Ab:placebo
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300mg
0.9% Saline
Buffer Solution
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Experimental: Group 2
Single agent, abdominal subcutaneous injection 10:2 ratio for Ab:placebo
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0.9% Saline
Buffer Solution
300mg
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Experimental: Group 3
Single agent intravenous injection 10:2 ratio for Ab:placebo
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300mg
0.9% Saline
Buffer Solution
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Experimental: Group 4
Single agent intravenous injection 10:2 ratio for Ab:placebo
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0.9% Saline
Buffer Solution
300mg
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Experimental: Group 5
Combined agent intravenous injection 10:2 ratio for Ab:placebo
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0.9% Saline
Buffer Solution
30mg/kg of each
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Experimental: Group 6
Subcutaneous injection combined ratio 1 with loading dose 30:3 ratio of Ab:Placebo
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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
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Experimental: Group 7
Subcutaneous injection in abdomen combined ratio 2 with loading dose 30:3 ratio of Ab:Placebo
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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
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Experimental: Group 8
Subcutaneous injection in abdomen combined ratio 3 with loading dose 30:3 ratio of Ab:Placebo
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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
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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
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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
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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
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92 Weeks
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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
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92 Weeks
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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
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92 Weeks
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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
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92 Weeks
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Serum concentration of anti-3BNC117-LS-J antibodies in each group at multiple timepoints.
Time Frame: 92 Weeks
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92 Weeks
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Serum concentration of anti-10-1074-LS-J antibodies in each group at multiple timepoints.
Time Frame: 92 Weeks
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92 Weeks
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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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