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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04173819
Recruitment Status : Unknown
Verified January 2020 by International AIDS Vaccine Initiative.
Recruitment status was:  Recruiting
First Posted : November 22, 2019
Last Update Posted : December 16, 2020
Sponsor:
Collaborators:
Fred Hutchinson Cancer Center
Rockefeller University
Brigham and Women's Hospital
Information provided by (Responsible Party):
International AIDS Vaccine Initiative

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.

Condition or disease Intervention/treatment Phase
HIV-1-infection Biological: 3BNC117-LS-J 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 Biological: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 225 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Safety and Pharmacokinetics of the Combination Broadly Neutralizing Antibodies, 3BNC117-LS-J and 10-1074-LS-J, in Healthy American and African Adults
Actual Study Start Date : January 25, 2019
Estimated Primary Completion Date : December 1, 2021
Estimated Study Completion Date : December 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Group 1
Single Agent, abdominal subcutaneous injection, 10:2 ratio for Ab:placebo
Biological: 3BNC117-LS-J
300mg

Biological: Placebo
Buffer Solution

Experimental: Group 2
Single agent, abdominal subcutaneous injection 10:2 ratio for Ab:placebo
Biological: 10-1074-LS-J
300mg

Biological: Placebo
Buffer Solution

Experimental: Group 3
Single agent intravenous injection 10:2 ratio for Ab:placebo
Biological: 3BNC117-LS-J
300mg

Biological: Placebo
0.9% Saline

Experimental: Group 4
Single agent intravenous injection 10:2 ratio for Ab:placebo
Biological: 10-1074-LS-J
300mg

Biological: Placebo
0.9% Saline

Experimental: Group 5
Combined agent intravenous injection 10:2 ratio for Ab:placebo
Biological: Combination 3BNC117-LS-J and 10-1074-LS-J
30mg/kg of each

Biological: Placebo
0.9% Saline

Experimental: Group 6
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
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

Biological: Placebo
Buffer Solution

Experimental: Group 7
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
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

Biological: Placebo
Buffer Solution

Experimental: Group 8
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
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

Biological: Placebo
Buffer Solution

Experimental: Group 9
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
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

Biological: Placebo
Buffer Solution

Experimental: Group 10
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
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

Biological: Placebo
Buffer Solution




Primary Outcome Measures :
  1. 1. Proportion of participants with solicited and treatment-related unsolicited adverse events and their duration. [ Time Frame: 92 Weeks ]
  2. 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 ]
  3. 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 ]
  4. 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 ]

Secondary Outcome Measures :
  1. Serum concentration of anti-3BNC117-LS-J antibodies in each group at multiple timepoints. [ Time Frame: 92 Weeks ]
  2. Serum concentration of anti-10-1074-LS-J antibodies in each group at multiple timepoints. [ Time Frame: 92 Weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04173819


Contacts
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Contact: Dagna Laufer, MD 212-328-7459 Dlaufer@iavi.org

Locations
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United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Lindsey Baden, MD       LBADEN@BWH.HARVARD.EDU   
United States, New York
The Rockefeller University Recruiting
New York, New York, United States, 10065
Contact: Marina Caskey, MD    212-327-7396    mcaskey@mail.rockefeller.edu   
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Contact: Kim Louis    425-610-6448    info@seattlevaccines.org   
Kenya
Partners in Health Research and Development Not yet recruiting
Thika, Kiambu, Kenya
Contact: Nelly Mugo, MMED       nwamba@csrtkenya.org   
Kenya AIDS Vaccine Initiative - Institute of Clinical Research Not yet recruiting
Nairobi, Kenya
Contact: Gaudensia Mutua, MD    +25472220417    gmutua@kaviunion.org   
Rwanda
Center for Family Health Research Not yet recruiting
Kigali, Rwanda
Contact: Etienne Karita, MD, MSc, MPH       EKarita@rzhrg-mail.org   
South Africa
Wits Reproductive Health and HIV Institute Not yet recruiting
Johannesburg, South Africa
Contact: Sinead Delaney-Moretlwe, MD       sdelaney@wrhi.ac.za   
Uganda
Uganda Virus Research Institute Not yet recruiting
Entebbe, Uganda
Contact: Brenda Okech, PhD       bokech@iavi.or.ug   
Infectious Diseases Institute Kasangati Not yet recruiting
Kampala, Uganda
Contact: Andrew Mujugira, MD       mujugira@uw.edu   
Sponsors and Collaborators
International AIDS Vaccine Initiative
Fred Hutchinson Cancer Center
Rockefeller University
Brigham and Women's Hospital
Investigators
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Study Chair: Marina Caskey, MD Rockefeller University
Additional Information:
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Responsible Party: International AIDS Vaccine Initiative
ClinicalTrials.gov Identifier: NCT04173819    
Other Study ID Numbers: IAVI C100
First Posted: November 22, 2019    Key Record Dates
Last Update Posted: December 16, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No