Sicurezza e farmacocinetica della combinazione di anticorpi ampiamente neutralizzanti, 3BNC117-LS-J e 10-1074-LS-J, in adulti sani americani e africani
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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
- Biologico: 3BNC117-LS-J
- Biologico: Placebo
- Biologico: Placebo
- Biologico: 10-1074-LS-J
- Biologico: Combination 3BNC117-LS-J and 10-1074-LS-J
- Biologico: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 1
- Biologico: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 2
- Biologico: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 3
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Luoghi di studio
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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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Kigali, Ruanda
- Center for Family Health Research
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Massachusetts
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Boston, Massachusetts, Stati Uniti, 02115
- Brigham and Women's Hospital
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New York
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New York, New York, Stati Uniti, 10065
- The Rockefeller University
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Washington
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Seattle, Washington, Stati Uniti, 98109
- Fred Hutchinson Cancer Research Center
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Johannesburg, Sud 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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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Prevenzione
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Doppio
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: Group 1
Single Agent, abdominal subcutaneous injection, 10:2 ratio for Ab:placebo |
300mg 0.9% Saline Buffer Solution |
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Sperimentale: Group 2
Single agent, abdominal subcutaneous injection 10:2 ratio for Ab:placebo |
0.9% Saline Buffer Solution 300mg |
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Sperimentale: Group 3
Single agent intravenous injection 10:2 ratio for Ab:placebo |
300mg 0.9% Saline Buffer Solution |
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Sperimentale: Group 4
Single agent intravenous injection 10:2 ratio for Ab:placebo |
0.9% Saline Buffer Solution 300mg |
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Sperimentale: 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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Sperimentale: 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 |
|
Sperimentale: 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 |
|
Sperimentale: 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 |
|
Sperimentale: 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 |
|
Sperimentale: 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 |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
|---|---|
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1. Proporzione di partecipanti con eventi avversi non richiesti sollecitati e correlati al trattamento e loro durata.
Lasso di tempo: 92 settimane
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92 settimane
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Proporzione di partecipanti con eventi avversi gravi (SAE) durante il periodo di studio che sono considerati correlati al prodotto sperimentale e alla loro durata.
Lasso di tempo: 92 settimane
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92 settimane
|
|
Concentrazione sierica di ciascun anticorpo in ciascun gruppo in più punti temporali insieme alle caratteristiche dei partecipanti (ad esempio sesso, peso e indice di massa corporea)
Lasso di tempo: 92 settimane
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92 settimane
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Il rapporto tra 3BNC117-LS-J e 10-1074-LS-J che, quando iniettato SC, manterrà livelli simili di ciascun bNAb allo stato stazionario.
Lasso di tempo: 92 settimane
|
92 settimane
|
Misure di risultato secondarie
Misura del risultato |
Lasso di tempo |
|---|---|
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Concentrazione sierica di anticorpi anti-3BNC117-LS-J in ciascun gruppo in più punti temporali.
Lasso di tempo: 92 settimane
|
92 settimane
|
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Concentrazione sierica di anticorpi anti-10-1074-LS-J in ciascun gruppo in più punti temporali.
Lasso di tempo: 92 settimane
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92 settimane
|
Collaboratori e investigatori
Investigatori
- Cattedra di studio: Marina Caskey, MD, Rockefeller University
Pubblicazioni e link utili
Collegamenti utili
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Altri numeri di identificazione dello studio
- IAVI C100
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Informazioni su farmaci e dispositivi, documenti di studio
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Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
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