Live Attenuated ETEC Vaccine ACE527 With and Without dmLT Adjuvant in Adults

Completed · Phase 1/Phase 2 · Has a placebo group

Conditions studied: Diarrhea

In brief

This is a research study about an experimental (investigational) oral ETEC vaccine (ACE527). ACE527 is a live attenuated vaccine that is being made to prevent disease from enterotoxigenic Escherichia coli (ETEC), which causes watery diarrhea, largely in children living in developing countries and in travelers to those countries. This research study is also testing an investigational adjuvant called dmLT. An adjuvant is something that is added to a vaccine to make it work better. The purpose of this study is two-fold. First, Part A aims to find out if the vaccine by itself or the vaccine combined with the adjuvant is safe, tolerable, and initiates an immune response. Second, Part B aims to find out if the vaccine by itself or the vaccine combined with the adjuvant prevents diarrheal disease when challenged with ETEC H10407. About 60 healthy adults, ages 18-50, will participate in Part A, and they will be required to stay in the research facility for several nights for the first dose, but will not be required to stay overnight for the second and third doses. Participants will be assigned to receive either the vaccine alone, the vaccine with adjuvant, or placebo by mouth. Study procedures include: stool samples, blood samples, and documentation of side effects. Participants will be involved in study related procedures for about 8 months. Interested volunteers from Part A will along with volunteers who were never vaccinated in Part A will return to participate in Part B. These volunteers will be required to stay overnight in the research facility for several nights after challenge, after which they will be treated with antibiotics and sent home. Study procedures include stool samples, blood samples, and documentation of infection with ETEC H10407. If the vaccine with/without adjuvant is effective, the volunteers should not development diarrhea, but if the vaccine with/without adjuvant is not effective, the volunteers will have diarrhea for a few days.

Key facts

Study ID

NCT01739231

Run by

PATH

People needed

81

Starts

2012-09-01

Expected to finish

2014-01-01

Last updated by the study team

2019-02-12

Who can join

Age: 18 and older, up to 50. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• Male and female healthy adults between 18 and 50 years of age at the time of enrollment.
• General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of PI.
• Negative pregnancy test at screening and before the first (V0), second (V28), and third vaccinations (V56) for female volunteers 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 volunteers 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 and knowledge of ETEC associated illness by passing a written examination (70% pass score).
• Availability for the study duration, including all planned follow-up visits.
• Received at least 2 doses of ACE527 vaccine alone or in combination with 25 ug dmLT 4-6 months prior to challenge (Part B only)

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, or serum chemistry as determined by PI or PI in consultation with the Medical Officer 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.
• Volunteers whose Body Mass Index (BMI) is less than 19.0 or greater than 34.0 (kg/m2)
• Recent vaccination or receipt of an investigational product (within 30 days before vaccination).
• Intention to donate blood or blood products within 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 volunteer 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 (≥ weekly) 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.
• 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 48hours prior to dosing.
• History of diarrhea in the 7 days prior to vaccination (outpatient diarrhea is defined as ≥ 3 unformed (grade 3 or greater) loose stools in 24 hours).
• Known allergy to two of the three following antibiotics: Ciprofloxacin, amoxicillin, and/or trimethoprim/sulfamethoxazole

Where it is running

• Center for Immunization Research (CIR) at Johns Hopkins School of Public Health (JHSPH) — Baltimore, Maryland, United States

Full record on ClinicalTrials.gov

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