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Safety and Efficacy Study of a Vaccine Against Enterotoxigenic Escherichia Coli (ETEC) to Prevent Moderate to Severe Diarrhea

4 de marzo de 2011 actualizado por: TD Vaccines A/S

Development of a Polyvalent Vaccine Against Enterotoxigenic Escherichia Coli (ETEC)Protective Efficacy of the Deletion-Attenuated, Multi-valent ACE527 Against Challenge With a Prototype Strain of Enterotoxigenic E.Coli Expressing LT and ST Enterotoxins and CFA/I (Strain H10407) in Human Challenge Model.

This is a research study about an experimental (investigational) vaccine called ACE527. ACE527 is a vaccine that is being made to prevent disease from a germ called enterotoxigenic Escherichia coli (ETEC). This germ causes diarrhea, largely in children living in developing countries and in travelers to those countries. One purpose of this study is to see if the vaccine is safe and develops an immune response. Another purpose is to see if it prevents people from getting sick when exposed to the ETEC germ. This ETEC germ is also experimental (investigational).

Descripción general del estudio

Estado

Terminado

Condiciones

Descripción detallada

This is a single-center, double-blind, placebo-controlled, Phase II vaccination and challenge study designed to assess the protective efficacy of the ACE 527 vaccine, as well as collect expanded safety and immunogenicity data. The study will be carried out in two phases. In the initial vaccination phase, up to 72 subjects will be randomized 1:1 to receive either ACE527 or placebo on an outpatient basis. Vaccine and placebo preparations will be given orally. Following vaccination, subjects will be followed as out-patients for safety using diary card surveillance, for vaccine shedding by qualitative stool culture (i.e. presence or absence) and for the development of local and systemic antibody responses to the ACE527 vaccine strains. In the subsequent inpatient challenge phase, up to 56 vaccinated subjects will be admitted as inpatients and challenged with the ETEC strain, H10407. The challenge dose will be administered orally.After challenge, subjects will be monitored for diarrhea and other signs/symptoms of enteric illness by daily medical checks, vital sign determinations, grading and weighing of all stools. Monitoring for fecal shedding of the challenge ETEC strain H10407 will occur daily, after challenge, while in-patient. Local and systemic antibody responses to the challenge ETEC strain H10407 will also be assessed. All subjects will be treated with Abx.

Tipo de estudio

Intervencionista

Inscripción (Actual)

70

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

    • Maryland
      • Baltimore, Maryland, Estados Unidos, 21205
        • Center for Immunization Research (CIR)

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

Sí

Géneros elegibles para el estudio

Todos

Descripción

Inclusion criteria:

  • Male or female age ≥18 and ≤ 50 years.
  • General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of PI.
  • Negative serum pregnancy test before first (visit V0) and before challenge (visit C0) for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable. Female subjects unable to bear children must have this documented (e.g. tubal ligation or hysterectomy) or must have negative pregnancy tests.
  • Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
  • Completion of a training session and demonstrated comprehension of the protocol procedures, knowledge of ETEC-associated illness, and by passing a written examination.
  • Availability for the study duration, including all planned follow-up visits.

Exclusion criteria:

  • Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study. Some medical conditions which are adequately treated and stable would not preclude entry into the study. These conditions might include stable asthma controlled with inhalers or mild hypertension stably controlled with a single agent.
  • Significant abnormalities in screening hematology, serum chemistry or urinalysis as determined by PI or PI in consultation with the MM and sponsor.
  • Presence in the serum of HIV antibody, HBsAg, or HCV antibody.
  • Evidence of IgA deficiency (serum IgA < 7 mg/dl or limit of detection of assay).
  • Evidence of current excessive alcohol consumption or drug dependence.
  • Evidence of impaired immune function.
  • BMI <19, >34
  • Recent vaccination or receipt of an investigational product (within 30 days before vaccination).
  • Intention to donate blood or blood products for one month following the completion of study participation (note: The Red Cross will not allow blood donations for 1 year following participation in an investigational research study).
  • Any other criteria which, in the investigator's opinion, would compromise the ability of the subject to participate in the study, the safety of the study, or the results of the study
  • Working as a food handler, in child-care or as a healthcare worker with direct patient contact.
  • Have household contacts who are <2 years old or >80 years old or infirm or immunocompromised (for reasons including corticosteroid therapy, HIV infection, cancer chemotherapy, or other chronic debilitating disease).
  • Abnormal stool pattern (fewer than 3 per week or more than 3 per day).
  • Regular use of laxatives, antacids, or other agents to lower stomach acidity.
  • Use of any medication known to affect the immune function (e.g., corticosteroids and others) within 30 days preceding the first vaccination or planned use during the active study period.
  • Known allergy to two of the following antibiotics: quinolones, trimethoprim-sulfamethoxazole, and penicillin.
  • Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within two years prior to dosing, OR planned travel to endemic countries during the length of the study.
  • Vaccination for or ingestion of ETEC, cholera, or LT toxin within 3 years prior to dosing.
  • Use of antibiotics during the 7 days before dosing or proton pump inhibitors, H2 blockers or antacids within 48 hours prior to dosing.
  • History of diarrhea in the 7 days prior to vaccination (outpatient diarrhea is defined as ≥ 3 unformed loose stools in 24 hours).

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: Doble

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: ACE527

First cohort: ACE527 vaccine doses of 9 x 10E10 cfu on study day 0 and 21 on an outpatient basis.

Second cohort: ACE527 vaccine dose of 9 x 10E10 cfu on study day 0 and 21 on an outpatient basis.

ACE527 comprises a mixture of three live, attenuated ETEC strains; ACAM2025 (CFA/I+ and LTB+), ACAM2022 (CS5+, CS6+ and LTB+), and ACAM2027 (CS1+, CS2+, CS3+ and LTB+). The vaccine is administered orally as a two-dose regimen, at 9x1010 cfu, on Days 0 and 21, in 200 ml CeraVacx buffer. The required volume of each vaccine strain, supplied as a frozen suspension, is mixed into the buffer solution prior to dosing.
Comparador de placebos: Placebo vaccine

First cohort: Placebo vaccine on study day 0 and 21 on an outpatient basis.

Second cohort: Placebo vaccine on study day 0 and 21 on an outpatient basis.

Placebo

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Periodo de tiempo
Severe diarrhea: ≥6 grade 3-5 stools in 24 hrs, or >800g of grade 3-5 stools in 24 hrs and moderate diarrhea: 4-5 grade 3-5 stools in 24 hrs or 401-800g of grade 3-5 stools in 24 hrs
Periodo de tiempo: Study Day 49 to 57
Study Day 49 to 57

Medidas de resultado secundarias

Medida de resultado
Periodo de tiempo
Number of subjects with severe diarrhea (if any)
Periodo de tiempo: Study Day 49 to 57
Study Day 49 to 57
Number of subjects with diarrhea of any severity
Periodo de tiempo: Study Day 49 to 57
Study Day 49 to 57
Mean total weight of grade 3-5 stools passed per subject
Periodo de tiempo: Study Day 49 to 57
Study Day 49 to 57
Mean number of grade 3-5 stools per subject
Periodo de tiempo: Study day 49 to 57
Study day 49 to 57
Number of subjects with nausea, vomiting, anorexia, or abdominal pain/cramps rated as moderate to severe.
Periodo de tiempo: Study Day 0 to 77
Study Day 0 to 77
Number of subjects who indicate they would have reduced their daily activity if they had been vacationing or traveling for business because of their ETEC illness.
Periodo de tiempo: Last visit
Last visit
Mean time to onset of diarrhea.
Periodo de tiempo: Study Day 49 to 57
Study Day 49 to 57
Number of subjects with moderate to severe ETEC illness
Periodo de tiempo: Study Day 49 to 57
Study Day 49 to 57
Number of colony forming unite (cfu) of the challenge strain per gram of stool
Periodo de tiempo: Study day 49 to 57
Study day 49 to 57
Number of subjects requiring early antibiotic treatment
Periodo de tiempo: Study Day 49 to 57
Study Day 49 to 57
Number of subjects requiring IV fluids
Periodo de tiempo: Study Day 49 to 57
Study Day 49 to 57
Systemic immune responses to the constituent strains of the vaccine
Periodo de tiempo: Selected Time Points
Selected Time Points
Mucosal immune responses to the constituent strains of the vaccine
Periodo de tiempo: Selected Time Points
Selected Time Points
The intestinal colonization by the three individual vaccine strains and challenge strain post-vaccination
Periodo de tiempo: Selected Time Points
Selected Time Points

Colaboradores e Investigadores

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

Patrocinador

Investigadores

  • Investigador principal: Clayton Harro, MD, CIR, Johns Hopkins School of Public Health

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 marzo de 2010

Finalización primaria (Actual)

1 de octubre de 2010

Finalización del estudio (Actual)

1 de octubre de 2010

Fechas de registro del estudio

Enviado por primera vez

28 de enero de 2010

Primero enviado que cumplió con los criterios de control de calidad

1 de febrero de 2010

Publicado por primera vez (Estimar)

2 de febrero de 2010

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

7 de marzo de 2011

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

4 de marzo de 2011

Última verificación

1 de marzo de 2011

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. .

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