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

Phase 2

Completed

• Conditions: Diarrhea
• Interventions: Biological: Placebo; Biological: ACE527

• Registration Number: NCT01060748
• Lead Sponsor: TD Vaccines A/S

Brief Summary

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).

Detailed Description

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.

Study Timeline

• Study First Submitted: 2010-01-28
• Study First Submitted QC: 2010-02-01
• Study First Posted: 2010-02-02
• Study Start: 2010-03
• Primary Completion: 2010-10
• Study Completion: 2010-10
• Status Verified: 2011-03
• Last Update Submitted: 2011-03-04
• Last Update Posted: 2011-03-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo vaccine	Placebo	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.
ACE527	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.

Primary Outcome Measures

Name	Time	Method
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	Study Day 49 to 57

Secondary Outcome Measures

Name	Time	Method
Mean time to onset of diarrhea.	Study Day 49 to 57
Number of colony forming unite (cfu) of the challenge strain per gram of stool	Study day 49 to 57
Systemic immune responses to the constituent strains of the vaccine	Selected Time Points
Number of subjects with severe diarrhea (if any)	Study Day 49 to 57
Number of subjects with moderate to severe ETEC illness	Study Day 49 to 57
Mean number of grade 3-5 stools per subject	Study day 49 to 57
The intestinal colonization by the three individual vaccine strains and challenge strain post-vaccination	Selected Time Points
Number of subjects with diarrhea of any severity	Study Day 49 to 57
Mean total weight of grade 3-5 stools passed per subject	Study Day 49 to 57
Number of subjects requiring early antibiotic treatment	Study Day 49 to 57
Number of subjects requiring IV fluids	Study Day 49 to 57
Number of subjects with nausea, vomiting, anorexia, or abdominal pain/cramps rated as moderate to severe.	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.	Last visit
Mucosal immune responses to the constituent strains of the vaccine	Selected Time Points

Trial Locations

Locations (1)

Center for Immunization Research (CIR); 🇺🇸 Baltimore, Maryland, United States