Veiligheid en farmacokinetiek van de combinatie van grotendeels neutraliserende antilichamen, 3BNC117-LS-J en 10-1074-LS-J, bij gezonde Amerikaanse en Afrikaanse volwassenen
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.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
- Biologisch: 3BNC117-LS-J
- Biologisch: Placebo
- Biologisch: Placebo
- Biologisch: 10-1074-LS-J
- Biologisch: Combination 3BNC117-LS-J and 10-1074-LS-J
- Biologisch: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 1
- Biologisch: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 2
- Biologisch: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 3
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
- Fase 1
Contacten en locaties
Studie Locaties
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Nairobi, Kenia
- Kenya AIDS Vaccine Initiative - Institute of Clinical Research
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Kiambu County
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Thika, Kiambu County, Kenia
- Partners in Health Research and Development
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Entebbe, Oeganda
- Uganda Virus Research Institute
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Kampala, Oeganda
- Infectious Diseases Institute Kasangati
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Kigali, Rwanda
- Center for Family Health Research
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Massachusetts
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Boston, Massachusetts, Verenigde Staten, 02115
- Brigham and Women's Hospital
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New York
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New York, New York, Verenigde Staten, 10065
- The Rockefeller University
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Washington
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Seattle, Washington, Verenigde Staten, 98109
- Fred Hutchinson Cancer Research Center
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Johannesburg, Zuid-Afrika
- Wits Reproductive Health and HIV Institute
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Preventie
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Dubbele
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: Group 1
Single Agent, abdominal subcutaneous injection, 10:2 ratio for Ab:placebo |
300mg 0.9% Saline Buffer Solution |
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Experimenteel: Group 2
Single agent, abdominal subcutaneous injection 10:2 ratio for Ab:placebo |
0.9% Saline Buffer Solution 300mg |
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Experimenteel: Group 3
Single agent intravenous injection 10:2 ratio for Ab:placebo |
300mg 0.9% Saline Buffer Solution |
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Experimenteel: Group 4
Single agent intravenous injection 10:2 ratio for Ab:placebo |
0.9% Saline Buffer Solution 300mg |
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Experimenteel: Group 5
Combined agent intravenous injection 10:2 ratio for Ab:placebo |
0.9% Saline Buffer Solution 30mg/kg of each |
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Experimenteel: 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 |
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Experimenteel: 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 |
|
Experimenteel: 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 |
|
Experimenteel: 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 |
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Experimenteel: 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 |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
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1. Percentage deelnemers met gevraagde en behandelingsgerelateerde ongevraagde bijwerkingen en de duur ervan.
Tijdsspanne: 92 weken
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92 weken
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Percentage deelnemers met ernstige bijwerkingen (SAE's) gedurende de onderzoeksperiode waarvan wordt aangenomen dat ze verband houden met het onderzoeksproduct en de duur ervan.
Tijdsspanne: 92 weken
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92 weken
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Serumconcentratie van elk antilichaam in elke groep op meerdere tijdstippen samen met kenmerken van de deelnemer (bijv. Geslacht, gewicht en BMI)
Tijdsspanne: 92 weken
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92 weken
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De verhouding van 3BNC117-LS-J tot 10-1074-LS-J die, wanneer SC geïnjecteerd, vergelijkbare niveaus van elk bNAb in stabiele toestand zal handhaven.
Tijdsspanne: 92 weken
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92 weken
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Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
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Serumconcentratie van anti-3BNC117-LS-J-antilichamen in elke groep op meerdere tijdstippen.
Tijdsspanne: 92 weken
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92 weken
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Serumconcentratie van anti-10-1074-LS-J-antilichamen in elke groep op meerdere tijdstippen.
Tijdsspanne: 92 weken
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92 weken
|
Medewerkers en onderzoekers
Onderzoekers
- Studie stoel: Marina Caskey, MD, Rockefeller University
Publicaties en nuttige links
Nuttige links
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Andere studie-ID-nummers
- IAVI C100
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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