Overview

This trial is active, not recruiting.

Condition escherichia coli infection
Treatments recombinant fimbrial adhesin dsc14cfae-scta2/ltb5, recombinant fimbrial adhesin dsccfae, modified e. coli heat labile enterotoxin ltr192g
Phase phase 1
Sponsor U.S. Army Medical Research and Materiel Command
Start date August 2012
End date November 2016
Trial size 57 participants
Trial identifier NCT01644565, 1924, NMRC.2012.0005, S-12-07

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose prevention
Arm
(Experimental)
Recombinant fimbrial adhesin dscCfaE: 1 ug of dscCfaE ID on study days 0, 21 and 42
recombinant fimbrial adhesin dsccfae dscCfaE
(Experimental)
Recombinant fimbrial adhesin dsc14CfaE-sCTA2/LTB5: 2.6 ug of Chimera ID on study days 0, 21 and 42
recombinant fimbrial adhesin dsc14cfae-scta2/ltb5 Chimera
(Experimental)
Modified E. coli heat labile enterotoxin LTR192G: 100 ng of LTR192G ID on study days 0, 21 and 42
modified e. coli heat labile enterotoxin ltr192g LTR192G
(Experimental)
Recombinant fimbrial adhesin dscCfaE and Modified E. coli heat labile enterotoxin LTR192G: 1 ug of dscCfaE + 100 ng of LTR192G ID on study days 0, 21 and 42
recombinant fimbrial adhesin dsccfae dscCfaE
modified e. coli heat labile enterotoxin ltr192g LTR192G
(Experimental)
Recombinant fimbrial adhesin dsc14CfaE-sCTA2/LTB5 and Modified E. coli heat labile enterotoxin LTR192G: 2.6 ug of Chimera + 100 ng of LTR192G ID on study days 0, 21 and 42
recombinant fimbrial adhesin dsc14cfae-scta2/ltb5 Chimera
modified e. coli heat labile enterotoxin ltr192g LTR192G
(Experimental)
Recombinant fimbrial adhesin dscCfaE and Modified E. coli heat labile enterotoxin LTR192G: 5 ug of dscCfaE + 100 ng of LTR192G ID on study days 0, 21 and 42
recombinant fimbrial adhesin dsccfae dscCfaE
modified e. coli heat labile enterotoxin ltr192g LTR192G
(Experimental)
Recombinant fimbrial adhesin dsc14CfaE-sCTA2/LTB5 and Modified E. coli heat labile enterotoxin LTR192G: 12.9 ug of Chimera + 100 ng of LTR192G ID on study days 0, 21 and 42
recombinant fimbrial adhesin dsc14cfae-scta2/ltb5 Chimera
modified e. coli heat labile enterotoxin ltr192g LTR192G
(Experimental)
Recombinant fimbrial adhesin dscCfaE and Modified E. coli heat labile enterotoxin LTR192G: 25 ug dscCfaE + 100 ng LTR192G ID on study days 0, 21 and 42
recombinant fimbrial adhesin dsccfae dscCfaE
modified e. coli heat labile enterotoxin ltr192g LTR192G
(Experimental)
Recombinant fimbrial adhesin dscCfaE and Modified E. coli heat labile enterotoxin LTR192G: TBD ug dscCfaE + 50 ng LTR192G TCI on study days 0, 21 and 42
recombinant fimbrial adhesin dsccfae dscCfaE
modified e. coli heat labile enterotoxin ltr192g LTR192G

Primary Outcomes

Measure
Number of Adverse Events
time frame: 1 year
Number of seroconversion events
time frame: day 0, 21, 42, 56, 70

Secondary Outcomes

Measure
Number of positive IgA-ASC response
time frame: Day 0, 21,42, 56, 70

Eligibility Criteria

Male or female participants from 18 years up to 45 years old.

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.

Additional Information

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
Principal investigator Ramiro L. Gutierrez, MD, MPH
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2015.
Information provided to ClinicalTrials.gov by U.S. Army Medical Research and Materiel Command.