Sikkerhet og farmakokinetikk av kombinasjonen bredt nøytraliserende antistoffer, 3BNC117-LS-J og 10-1074-LS-J, hos friske amerikanske og afrikanske voksne
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.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
- Biologisk: 3BNC117-LS-J
- Biologisk: Placebo
- Biologisk: Placebo
- Biologisk: 10-1074-LS-J
- Biologisk: Combination 3BNC117-LS-J and 10-1074-LS-J
- Biologisk: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 1
- Biologisk: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 2
- Biologisk: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 3
Studietype
Registrering (Faktiske)
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Studiesteder
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Massachusetts
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Boston, Massachusetts, Forente stater, 02115
- Brigham and Women's Hospital
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New York
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New York, New York, Forente stater, 10065
- The Rockefeller University
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Washington
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Seattle, Washington, Forente stater, 98109
- Fred Hutchinson Cancer Research Center
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-
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-
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Nairobi, Kenya
- Kenya AIDS Vaccine Initiative - Institute of Clinical Research
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Kiambu County
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Thika, Kiambu County, Kenya
- Partners in Health Research and Development
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-
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Kigali, Rwanda
- Center for Family Health Research
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-
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Johannesburg, Sør-Afrika
- Wits Reproductive Health and HIV Institute
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-
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Entebbe, Uganda
- Uganda Virus Research Institute
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Kampala, Uganda
- Infectious Diseases Institute Kasangati
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Forebygging
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Dobbelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Group 1
Single Agent, abdominal subcutaneous injection, 10:2 ratio for Ab:placebo |
300mg 0.9% Saline Buffer Solution |
|
Eksperimentell: Group 2
Single agent, abdominal subcutaneous injection 10:2 ratio for Ab:placebo |
0.9% Saline Buffer Solution 300mg |
|
Eksperimentell: Group 3
Single agent intravenous injection 10:2 ratio for Ab:placebo |
300mg 0.9% Saline Buffer Solution |
|
Eksperimentell: Group 4
Single agent intravenous injection 10:2 ratio for Ab:placebo |
0.9% Saline Buffer Solution 300mg |
|
Eksperimentell: Group 5
Combined agent intravenous injection 10:2 ratio for Ab:placebo |
0.9% Saline Buffer Solution 30mg/kg of each |
|
Eksperimentell: 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 |
|
Eksperimentell: 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 |
|
Eksperimentell: 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 |
|
Eksperimentell: 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 |
|
Eksperimentell: 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 |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
1. Andel deltakere med oppfordrede og behandlingsrelaterte uønskede uønskede hendelser og deres varighet.
Tidsramme: 92 uker
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92 uker
|
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Andel deltakere med alvorlige bivirkninger (SAE) i løpet av studieperioden som anses relatert til undersøkelsesproduktet og deres varighet.
Tidsramme: 92 uker
|
92 uker
|
|
Serumkonsentrasjon av hvert antistoff i hver gruppe på flere tidspunkter sammen med deltakerkarakteristikker (f.eks. kjønn, vekt og BMI)
Tidsramme: 92 uker
|
92 uker
|
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Forholdet mellom 3BNC117-LS-J og 10-1074-LS-J som, når det injiseres SC, vil opprettholde lignende nivåer av hver bNAb ved steady state.
Tidsramme: 92 uker
|
92 uker
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Serumkonsentrasjon av anti-3BNC117-LS-J antistoffer i hver gruppe på flere tidspunkter.
Tidsramme: 92 uker
|
92 uker
|
|
Serumkonsentrasjon av anti-10-1074-LS-J-antistoffer i hver gruppe på flere tidspunkter.
Tidsramme: 92 uker
|
92 uker
|
Samarbeidspartnere og etterforskere
Samarbeidspartnere
Etterforskere
- Studiestol: Marina Caskey, MD, Rockefeller University
Publikasjoner og nyttige lenker
Hjelpsomme linker
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
- IAVI C100
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
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