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

NCT01060748 | Completed Phase 2 DMC

• 1 other identifier: ACE527-102
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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).

Conditions

Diarrhea

Keywords

Vaccination; Challenge; Diarrhea; ETEC illness; Travelers diarrhea; ETEC; Enterotoxigenic E.coli

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Number of subjects with severe diarrhea (if any)

  Study Day 49 to 57

• 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

• Mean number of grade 3-5 stools per subject

  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

Study Arms (2)

ACE527

EXPERIMENTAL

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.

Biological: ACE527

Placebo vaccine

PLACEBO COMPARATOR

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.

Biological: Placebo

Interventions

ACE527 BIOLOGICAL

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.

ACE527

Placebo BIOLOGICAL

Placebo

Placebo vaccine

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• TD Vaccines A/S: lead
• Pierrel Research USA, Inc.: collaborator
• Johns Hopkins Bloomberg School of Public Health: collaborator

Study Sites (1)

Center for Immunization Research (CIR)

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Conditions

Diarrhea

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Clayton Harro, MD

  CIR, Johns Hopkins School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 28, 2010
• First Posted: February 2, 2010
• Study Start: March 1, 2010
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: March 7, 2011

Record last verified: 2011-03

Locations

US (1)