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Safety and Immunogenicity Study of tgAAC09, an HIV Vaccine in an Adeno-associated Virus (AAV) Capsid (TGC14F)

13 de diciembre de 2012 actualizado por: International AIDS Vaccine Initiative

Phase II, Placebo-controlled, Double-blind, Dose-escalation/Dose-optimization Trial to Evaluate Safety and Immunogenicity of tgAAC09, an HIV Vaccine Containing Clade C Gag-PR-ΔRT DNA in an Adeno-associated Virus (AAV) Capsid

This phase 2 study will evaluate the safety, immunogenicity and optimal timing of two injections at three dose levels of the tgAAC09 vaccine in healthy volunteers. Study volunteers will receive two intramuscular injections of tgAAC09 or placebo at Months 0 and 6 (groups A, C, E and G) or at Months 0 and 12 (groups B, D and F) and be followed for a total of 18 months following the first injection with the exception of group G in which volunteers will be followed for 12 months after the first injection (6 months after the second injection). This study will explore whether boosting is possible, and compare a shorter and more practical six-month time interval with a twelve-month time interval.

Descripción general del estudio

Descripción detallada

The study design will also assess the effect of the presence of anti-AAV2 capsid neutralizing antibodies at the time of vaccination on the safety and immunogenicity of tgAAC09. Since the prevalence of pre-existing neutralizing antibodies to AAV2 capsid is high (IAVI and Targeted Genetics, data on file), this protocol amendment adds Group G which is composed of volunteers who have documented pre-existing anti-AAV2 capsid neutralizing antibodies titers ≤ 1/8. This will assure that there are sufficient numbers of volunteers with and without antibodies for a useful comparison.

Tipo de estudio

Intervencionista

Inscripción (Actual)

91

Fase

  • Fase 2

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

      • Cape Town, Sudáfrica, 7920
        • Desmond Tutu HIV Centre Cape Town
      • South Africa, Sudáfrica, 0204
        • Medunsa
      • Soweto, Sudáfrica, 2013
        • Perinatal HIV Research Unit, Baragwanath Hospital
      • Entebbe, Uganda
        • Uganda Virus Research Institute
      • Lusaka, Zambia
        • Zambia-Emory HIV Research Project (ZEHRP)

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 50 años (Adulto)

Acepta Voluntarios Saludables

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Healthy male or female
  • Age at least 18 years on the day of screening and no greater than 50 years on the day of the first study injection
  • Willing to comply with the requirements of the protocol and available for follow up for the planned duration of the study
  • Able and willing to give informed consent.
  • Willing to undergo HIV testing, counseling and receive results
  • If sexually active female of child-bearing potential (not menopausal or anatomically sterile), willing to use an effective method of contraception (hormonal contraceptives; intrauterine contraceptive device (IUCD); condoms; anatomical sterility in self or partner) from screening until at least four months after last study injection and willing to undergo urine pregnancy tests at screening, prior to each injection and four months after the last injection
  • If sexually active male, willing to use a method of contraception (such as condoms) from screening until four months after the last study injection

Exclusion Criteria:

  • HIV-1 or HIV-2 infection
  • Active tuberculosis
  • Clinically relevant abnormality on history or examination including history of immunodeficiency, or cancer, or autoimmune disorder
  • Use of systemic corticosteroids, immunosuppressive or anticancer medications in the last six months
  • Chronic condition that, in the opinion of the investigator or the designated trial physician, would make the volunteer unsuitable for the study
  • Any of the following abnormal laboratory parameters:

    • Hemoglobin <9.0 g/dL (females), <12.0 g/dL (males)
    • Absolute Neutrophil Count (ANC): ≤ 999/mm3
    • Absolute Lymphocyte Count (ALC): ≤ 500/mm3
    • Platelets: decreased ≤ 90,000 or increased ≥ 550,000/mm3
    • Creatinine: > 1.4 x ULN
    • AST: >3.0 x ULN
    • ALT: >3.0 x ULN
    • Urine dipstick: blood = 2+ or more (except in menstruating females); protein = 2+ or more
  • Any of the following high-risk behaviors:

    • Had unprotected vaginal or anal sex with a known HIV positive person in the past six months
    • Had unprotected vaginal or anal sex with a casual partner (i.e. no continuing established relationship) in the past six months
    • Engaged in sex work for money or drugs in the past six months
    • Used injection drugs illegally in the past six months
    • Acquired a sexually transmitted infection (STI) in the past six months
  • If female, pregnant, lactating or planning a pregnancy within four months after last study injection
  • Receipt of live attenuated vaccine within 30 days or other vaccine within 14 days of the first study injection
  • Receipt of blood transfusion or blood products six months prior to the first study injection
  • Participation in another clinical trial of an investigational product currently or within last 12 weeks of first study injection or expected participation during this study
  • Prior receipt of an investigational HIV vaccine
  • History of severe local or systemic reaction to vaccination(s) or history of severe allergic reactions
  • History of major neurological or psychiatric disorders
  • Positive for hepatitis B surface antigen, active untreated syphilis (confirmed by treponemal test such as TPHA in addition to nontreponemal test such as RPR) or other active sexually transmitted diseases

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
Experimental: Group A

Number of Vaccine Recipients: 10

Dosage level 3 x 10^10 DRP

Month 0 + 6

Experimental: Group B

Number of Vaccine Recipients: 10

Dosage level 3 x 10^10 DRP

Month 0+12

Experimental: Group C

Number of Vaccine Recipients: 10

Dosage level 3 x 10^11 DRP

Month 0+6

Experimental: Group D

Number of Vaccine Recipients: 10

Dosage level 3 x 10^11 DRP

Month 0+12

Experimental: Group E

Number of Vaccine Recipients: 10

Dosage level 3 x 10^12 DRP

Month 0+6

Experimental: Group F

Number of Vaccine Recipients: 10

Dosage level 3 x 10^12 DRP

Month 0+12

Experimental: Group G

Number of Vaccine Recipients: 10

Preselected for baseline AAV neutralization titers of <1/8

Dosage level 3 x 10^12 DRP

Month 0+6

Comparador de placebos: Placebo
3 volunteers will receive placebo matched to each experimental group.
Sterile isotonic buffered salt solution

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Periodo de tiempo
Safety: proportion of volunteers with severe local and systemic reactions, proportion of volunteers with other SAEs (including laboratory abnormalities) related to study vaccine, number of volunteers with SAEs related to study vaccine
Periodo de tiempo: 18 months
18 months
Proportion of volunteers with HIV-1 specific T- cell responses quantified by γ-IFN ELISPOT and magnitude of the response, and proportion of volunteers with HIV-1 specific binding antibodies and magnitude of the response
Periodo de tiempo: 18 months
18 months

Medidas de resultado secundarias

Medida de resultado
Periodo de tiempo
Safety: high versus low or negative titres of neutralizing antibodies to AAV2 at the time of each vaccination
Periodo de tiempo: 18 months
18 months
Immunogenicity: proportion of volunteers with HIV-1 specific T- cell responses by γ-IFN CFC or other T-cell assays
Periodo de tiempo: 18 months
18 months
Immunogenicity endpoints in volunteers with high versus low or negative titres of neutralizing antibodies to AAV2 at the time of each vaccination
Periodo de tiempo: 18 months
18 months
Immunogenicity endpoints in volunteers with versus without four-fold or greater increase in titres of neutralizing antibodies to AAV2 after vaccination
Periodo de tiempo: 18 months
18 months
Immunogenicity endpoints after the second study injection, compared with the first study injection
Periodo de tiempo: 18 months
18 months
Immunogenicity endpoints after the second study injection following a twelve-month interval compared to a six-month interval
Periodo de tiempo: 18 months
18 months
Vaccine biodistribution: presence and persistence of vaccine in peripheral blood mononuclear cells (PBMC), saliva, nasal swabs, urine and semen or cervical/vaginal secretions
Periodo de tiempo: 18 months
18 months

Colaboradores e Investigadores

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

Investigadores

  • Silla de estudio: Eftyhia Vardas, MD, Perinatal HIV Research Unit (PHRU), Baragwanath
  • Investigador principal: Linda-Gail Bekker, MD, Desmond Tutu HIV Centre Cape Town
  • Investigador principal: Anwar Hoosen, Medical University of Southern Africa (Medunsa)
  • Investigador principal: Elwyn Chomba, MD, Zambia-Emory HIV Research Project (ZEHRP), Lusaka
  • Investigador principal: Pontiano Kaleebu, MD, PhD, MRC/UVRI and LSHTM Uganda Research Unit

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.

Enlaces Útiles

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 octubre de 2005

Finalización primaria (Actual)

1 de diciembre de 2007

Finalización del estudio (Actual)

1 de diciembre de 2007

Fechas de registro del estudio

Enviado por primera vez

23 de abril de 2009

Primero enviado que cumplió con los criterios de control de calidad

24 de abril de 2009

Publicado por primera vez (Estimar)

27 de abril de 2009

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

17 de diciembre de 2012

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

13 de diciembre de 2012

Última verificación

1 de diciembre de 2012

Más información

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. .

Ensayos clínicos sobre Infecciones por VIH

Ensayos clínicos sobre tgAAC09

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