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

HIV-1-infection Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04173819
• Other study ID #: IAVI C100
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: January 25, 2019
• Est. completion date: September 2023

Study information

• Verified date: March 2023
• Source: International AIDS Vaccine Initiative
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 225
• Est. completion date: September 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Biological:
• 3BNC117-LS-J
300mg
• 10-1074-LS-J
300mg
• Combination 3BNC117-LS-J and 10-1074-LS-J
30mg/kg of each
• 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
• 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
• 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
• Placebo
0.9% Saline
• Placebo
Buffer Solution

Locations

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

Sponsors (4)

Lead Sponsor	Collaborator
International AIDS Vaccine Initiative	Brigham and Women's Hospital, Fred Hutchinson Cancer Center, Rockefeller University

Countries where clinical trial is conducted

United States,  Kenya,  Rwanda,  South Africa,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1. Proportion of participants with solicited and treatment-related unsolicited adverse events and their duration.		92 Weeks
Primary	Proportion of participants with serious adverse events (SAEs) throughout the study period that are considered related to investigational product and their duration.		92 Weeks
Primary	Serum concentration of each antibody in each group at multiple timepoints along with participant characteristics (e.g. sex, weight, and BMI)		92 Weeks
Primary	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	Serum concentration of anti-3BNC117-LS-J antibodies in each group at multiple timepoints.		92 Weeks
Secondary	Serum concentration of anti-10-1074-LS-J antibodies in each group at multiple timepoints.		92 Weeks

External Links

•   Related Info