Seguridad y farmacocinética de la combinación de anticuerpos ampliamente neutralizantes, 3BNC117-LS-J y 10-1074-LS-J, en adultos estadounidenses y africanos sanos
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
- Biológico: 3BNC117-LS-J
- Biológico: Placebo
- Biológico: Placebo
- Biológico: 10-1074-LS-J
- Biológico: Combination 3BNC117-LS-J and 10-1074-LS-J
- Biológico: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 1
- Biológico: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 2
- Biológico: Combination 3BNC117-LS-J and 10-1074-LS-J Ratio 3
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02115
- Brigham and Women's Hospital
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New York
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New York, New York, Estados Unidos, 10065
- The Rockefeller University
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Washington
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Seattle, Washington, Estados Unidos, 98109
- Fred Hutchinson Cancer Research Center
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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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Kigali, Ruanda
- Center for Family Health Research
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Johannesburg, Sudáfrica
- 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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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Group 1
Single Agent, abdominal subcutaneous injection, 10:2 ratio for Ab:placebo |
300mg 0.9% Saline Buffer Solution |
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Experimental: Group 2
Single agent, abdominal subcutaneous injection 10:2 ratio for Ab:placebo |
0.9% Saline Buffer Solution 300mg |
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Experimental: Group 3
Single agent intravenous injection 10:2 ratio for Ab:placebo |
300mg 0.9% Saline Buffer Solution |
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Experimental: Group 4
Single agent intravenous injection 10:2 ratio for Ab:placebo |
0.9% Saline Buffer Solution 300mg |
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Experimental: 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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Experimental: 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 |
|
Experimental: 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 |
|
Experimental: 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 |
|
Experimental: 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 |
|
Experimental: 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 |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
|
1. Proporción de participantes con eventos adversos solicitados y no solicitados relacionados con el tratamiento y su duración.
Periodo de tiempo: 92 semanas
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92 semanas
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Proporción de participantes con eventos adversos graves (SAE) a lo largo del período de estudio que se consideran relacionados con el producto en investigación y su duración.
Periodo de tiempo: 92 semanas
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92 semanas
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Concentración sérica de cada anticuerpo en cada grupo en múltiples puntos de tiempo junto con las características de los participantes (p. ej., sexo, peso e IMC)
Periodo de tiempo: 92 semanas
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92 semanas
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La proporción de 3BNC117-LS-J a 10-1074-LS-J que, cuando se inyecta SC, mantendrá niveles similares de cada bNAb en estado estacionario.
Periodo de tiempo: 92 semanas
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92 semanas
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Concentración sérica de anticuerpos anti-3BNC117-LS-J en cada grupo en múltiples puntos de tiempo.
Periodo de tiempo: 92 semanas
|
92 semanas
|
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Concentración sérica de anticuerpos anti-10-1074-LS-J en cada grupo en múltiples puntos de tiempo.
Periodo de tiempo: 92 semanas
|
92 semanas
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Silla de estudio: Marina Caskey, MD, Rockefeller University
Publicaciones y enlaces útiles
Enlaces Útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Otros números de identificación del estudio
- IAVI C100
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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