Clinical trial NCT01644565: Safety Study of Chimeric Vaccine to Prevent ETEC Diarrhea
Official title: A Phase 1 Dose Escalating Study of Two Enterotoxigenic Escherichia Coli Prototype Adhesin-based Vaccines With or Without Modified Heat-labile Enterotoxin by Intradermal or Transcutaneous Immunization
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Escherichia Coli Infection
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
First posted: 2012-07-19
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of the study is to determine if immunization with a chimeric E. coli protein, dsc14CfaE-sCT2/LTB5, is safe and immunogenic when administered by vaccination under the skin.

Detailed description: The purpose of the study is to evaluate the safety and immunogenicity of dsc14cfaEsCTA2/LTB5 (Chimera) and dscCfaE administered with and without LTR192G by intradermal (ID) immunization and to gather additional data on the administration of dsCfaE and LTR192G via transcutaneous immunization (TCI) route. If vaccines are found to be safe and adequately immunogenic in humans, a down-selection would occur and a phase 2b vaccination/challenge study would be undertaken to further evaluate vaccine safety and allow a preliminary assessment of efficacy of one of these candidates by the ID or TCI route. With favorable evidence for safety, immunogenicity, efficacy, complemented by advances in standard methodology to combine multiple adhesins with an appropriate LT enterotoxoid form, a multivalent vaccine would be constructed and evaluated for further clinical development.

Eligibility criteria: Inclusion Criteria:

* Healthy, adult, male or female, age 18 to 45 years (inclusive) at the time of enrollment.
* Completion and review of comprehension test (achieved \> 70% accuracy).
* Signed informed consent document.
* Available for the required follow-up period and scheduled clinic visits.
* Women: Negative pregnancy test with understanding (through informed consent process) to not become pregnant during the study or within three (3) months following study completion.

Exclusion Criteria:

* Health problems (for example, chronic medical conditions such as psychiatric conditions, diabetes mellitus, hypertension or any other conditions that might place the subjects at increased risk of adverse events. Study clinicians, in consultation with the PI, will use clinical judgment on a case-by-case basis to assess safety risks under this criterion. The PI will consult with the Research Monitor as appropriate.
* Clinically significant abnormalities on physical examination.
* Use of immunosuppressive medications (systemic corticosteroids or chemotherapeutics that may influence antibody development), or immunosuppressive illness, including IgA deficiency (defined by serum IgA below the detectable limit).
* Women who are pregnant or planning to become pregnant during the study period plus 3 months beyond the last study safety visit and currently nursing women.
* Participation in research involving another investigational product (defined as receipt of investigational product or exposure to invasive investigational device) 30 days before planned date of first vaccination or anytime through the last study safety visit.
* Positive blood test for HBsAg, HCV, HIV-1.
* Clinically significant abnormalities on basic laboratory screening.
* Exclusionary skin history/findings that would confound assessment or prevent appropriate local monitoring of AEs, or possibly increase the risk of an AE.
* History of chronic skin disease (clinician judgment).
* History of atopy such as active eczema.
* Acute skin infection/eruptions on the upper arms including fungal infections, severe acne or active contact dermatitis.
* Allergies that may increase the risk of AEs.
* Regular use (weekly or more often) of antidiarrheal, anti-constipation, or antacid therapy.
* Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on a regular basis; loose or liquid stools on other than an occasional basis.
* Prior exposure to ETEC or Vibrio cholera.
* History of microbiologically confirmed ETEC or cholera infection.
* Travel to countries where ETEC or V. cholera or other enteric infections are endemic (most of the developing world) within two years prior to dosing clinician judgment).
* Received previous experimental ETEC or V. cholera vaccine or live ETEC or V. cholera challenge.
* Occupation involving handling of ETEC or V. cholera currently, or in the past 3 years.

Primary outcomes:
measure: Safety - Occurrence of Adverse Events
timeFrame: 1 year
Secondary outcomes:
measure: Number of Participants With Immune Responses to Vaccine Antigens
timeFrame: baseline and post dose
measure: Antigen-Specific IgA Geometric Mean Titers
timeFrame: Day 0, 21,42, 56, 70
Other outcomes:
Locations:
city: Silver Spring
country: United States
facility: Walter Reed Army Institute of Research Clinical trial Center
state: Maryland
Study officials:
affiliation: Enteric Diseases Department, Naval Medical Research Center
name: Ramiro L. Gutierrez, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: