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A Study to Evaluate Safety and Immunogenicity of AERAS-402 Administered in HIV-negative, BCG-vaccinated, QFT (+) and (-) Adults Without Evidence of TB (C-012-402)

25 de abril de 2016 actualizado por: Aeras

A Phase I Randomized Placebo-controlled Double-blind Study to Evaluate Safety and Immunogenicity of AERAS-402 Administered in HIV-negative, BCG-vaccinated, QuantiFERON®-TB Gold (+) and QuantiFERON®-TB Gold (-) Adults Without Evidence of Tuberculosis.

The available live tuberculosis vaccine Bacillus Calmette-Guérin (BCG) provides incomplete protection against pulmonary tuberculosis. For unknown reasons, a BCG revaccination or "booster", while not toxic, does not provide much additional protection. AERAS-402 presents tuberculosis antigens in the setting of a new, live, replication deficient adenovirus vaccine that may increase T cell immunity and thus protection from tuberculosis. Since BCG-vaccinated individuals are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to individuals in Kenya who have already been vaccinated with BCG.

Descripción general del estudio

Estado

Terminado

Condiciones

Descripción detallada

This Phase I study will be conducted as a double-blind, randomized, placebo-controlled study in 20 healthy adult subjects. The study will enroll 10 subjects who are QFT-G positive at screening and 10 subjects who are QFT-G negative at screening. Within QFT-G group, subjects will be randomized to receive AERAS-402 or placebo in a ratio of 4:1. One dose level of AERAS-402 (3 x 10^10 vp) will be investigated in this study. All subjects will receive a single dose of study vaccine (AERAS-402 or placebo) on Study Day 0 and a second dose of study vaccine (AERAS-402 or placebo) on Study Day 56. All vaccinations will be administered by IM injection into the deltoid muscle.

The sample size was selected as adequate for preliminary safety evaluations and initial immunogenicity reviews for this phase study, rather than for statistical reasons. If no serious adverse events are observed in 16 subjects who receive AERAS-402, the upper bound of the 95% confidence interval on the rate of serious adverse event occurrence is 17.1 percent.

The selection of AERAS-402 dose level for evaluation in this study was derived from animal studies and based on the safety profile for the completed and ongoing clinical studies in the U.S. and South Africa.The total duration of follow-up is 182 days for each subject with a total of eleven follow-up clinic visits. The study is planned at a single site in Kisumu, Kenya.

Tipo de estudio

Intervencionista

Inscripción (Actual)

20

Fase

  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

      • Kisumu, Kenia
        • Kenya Medical Research Institute

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 45 años (Adulto)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  1. Is male or female
  2. Is age 18 through 45 years on Study Day 0
  3. Has completed the written informed consent process
  4. Had BCG vaccination at least 5 years ago, documented through medical history or presence of scar
  5. Females: Ability to avoid pregnancy from 28 days prior to administration of the study vaccine through the end of the study.
  6. Has general good health, confirmed by medical history and physical examination.
  7. Has Body Mass Index (BMI) between 18 and 30 (wt./ht.2) by nomogram
  8. Has ability to complete follow-up period of 182 days as required by the protocol
  9. Is able and willing to commit to avoiding elective surgery for the duration of the study.
  10. Is able and willing to stay in contact with the study site for the duration of the study.
  11. Has completed simultaneous enrollment in Aeras Vaccine Development Registry Protocol.

Exclusion Criteria:

  1. Acute illness on the day of randomization.
  2. Fever ≥37.5°C on the day of randomization.
  3. Evidence of any significant active infection on the day of randomization.
  4. Used immunosuppressive medication within 45 days before entry into the study (inhaled and topical corticosteroids are permitted).
  5. Received immunoglobulin or blood products within 45 days before entry into the study.
  6. Received any investigational drug therapy or vaccine within 182 days before the first dose of study vaccine in this protocol.
  7. Received any standard vaccine within 45 days before the first dose of study vaccine in this protocol, through the last study visit (the use of licensed drugs or vaccines medically indicated during the study is permitted).
  8. Received any adenovector based vaccine previously.
  9. Current chronic drug therapy including hormones such as thyroxin, insulin, etc. (Estrogen and progesterone replacement and contraceptives are permitted)
  10. History or laboratory evidence of any past, present or future possible immunodeficiency state which will include, but is not limited to, any laboratory indication of HIV-1 infection.
  11. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine.
  12. Previous medical history that may compromise the safety of the subject in the study.
  13. Evidence of a new acute illness that may compromise the safety of the subject in the study.
  14. Pregnant or lactating/nursing females.
  15. Evidence of chronic hepatitis including a positive test for hepatitis B core antibody, or hepatitis C antibody.
  16. Inability to discontinue daily medications except contraceptives during the study.
  17. History of alcohol or drug abuse within the past 2 years.
  18. Tobacco or cannabis smoking three or more days per week
  19. Positive urine test for illicit drugs (opiates, cocaine, amphetamines).
  20. History or evidence of any systemic disease on physical examination or any acute or chronic illness that may interfere with the evaluation of the safety or immunogenicity of the vaccine, including axillary lymphadenopathy
  21. History or evidence (including chest X-ray) of active or past tuberculosis
  22. Abnormal hemoglobin, hematocrit, white blood cell count, absolute neutrophil count, absolute lymphocyte count, PT, PTT, GGT, ALT, AST, total bilirubin, ALP, and creatinine drawn within 36 hours of randomization. CPK must be drawn but the CPK value is not an exclusion criteria.
  23. History of high risk sexual behaviors.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Prevención
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador de placebos: Placebo
1.0 mL sterile buffer administered by intramuscular (IM) injection to deltoid area on days 0 and 56.
This is the identical buffer solution in which AERAS-402 is formulated.
Experimental: AERAS-402
1.0 mL containing 3 x 10^10 vp/mL suspended in 20 mM Tris buffer, 2 mM MgCl2, 25 mM NaCl, 10% w/v sucrose, 0.02% w/v PS-80 (polysorbate-80, non-animal source) and water. Administered intramuscular (IM) injection to deltoid area on days 0 and 56.
Given to 8 participants that were QFT-G(-) at screening and 8 participants that were GFT-G(+) at screening.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Safety of AERAS-402 in healthy, HIV-negative, BCG-vaccinated, QuantiFERON®-TB Gold In-Tube test (QFT-G)(+) and QFT-G(-) adults without evidence of tuberculosis disease in Kenya.
Periodo de tiempo: Day 0 thru Day 182
Collection of solicited and unsolicited adverse events.
Day 0 thru Day 182

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Immunogenicity profile of AERAS-402 in healthy, HIV-negative, BCG-vaccinated, QFT-G(+) and QFT-G(-) adults without evidence of tuberculosis disease in Kenya.
Periodo de tiempo: Day 0 thru day 182
Percentage of CD4 and CD8 T cells that produce any of three cytokines (IFN-γ, TNF-α, and/or IL-2) or a combination of the three cytokines simultaneously.
Day 0 thru day 182

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Investigadores

  • Investigador principal: Doug Walsh, MD, U. S. Army Medical Research Unit- Kenya

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de septiembre de 2008

Finalización primaria (Actual)

1 de junio de 2009

Finalización del estudio (Actual)

1 de julio de 2010

Fechas de registro del estudio

Enviado por primera vez

27 de abril de 2015

Primero enviado que cumplió con los criterios de control de calidad

29 de abril de 2015

Publicado por primera vez (Estimar)

30 de abril de 2015

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

27 de abril de 2016

Última actualización enviada que cumplió con los criterios de control de calidad

25 de abril de 2016

Última verificación

1 de abril de 2016

Más información

Términos relacionados con este estudio

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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