Safety Study of Chimeric Vaccine to Prevent ETEC Diarrhea

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01644565
First received: July 11, 2012
Last updated: July 8, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Escherichia Coli Infection
Biological: Recombinant fimbrial adhesin dsc14CfaE-sCTA2/LTB5
Biological: Recombinant fimbrial adhesin dscCfaE
Biological: Modified E. coli heat labile enterotoxin LTR192G
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase 1 Study of Two Enterotoxigenic Escherichia Coli Prototype Adhesin-Based Vaccines With or Without Modified Heat-labile Enterotoxin by Intradermal or Transcutaneous Immunization

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Safety Based on Number of Adverse Events [ Time Frame: Study Days 0 -180 ] [ Designated as safety issue: Yes ]
    Safety and tolerability as measured by occurrance of local and systemic adverse events following receipt of the investigational products


Secondary Outcome Measures:
  • Immunogenicity Based on Serum and Mucosal Responses [ Time Frame: Study Days 0 - 70 ] [ Designated as safety issue: No ]
    Development of systemic and mucosal immune responses as measured by serum and fecal antibody titers to the immunizing antigens as well as vaccine-specific antibody secreting cells.


Estimated Enrollment: 57
Study Start Date: August 2012
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A-1
Recombinant fimbrial adhesin dscCfaE: 1 ug of dscCfaE ID on study days 0, 21 and 42
Biological: Recombinant fimbrial adhesin dscCfaE
Other Name: dscCfaE
Experimental: Group A-2
Recombinant fimbrial adhesin dsc14CfaE-sCTA2/LTB5: 2.6 ug of Chimera ID on study days 0, 21 and 42
Biological: Recombinant fimbrial adhesin dsc14CfaE-sCTA2/LTB5
Other Name: Chimera
Experimental: Group A-3
Modified E. coli heat labile enterotoxin LTR192G: 100 ng of LTR192G ID on study days 0, 21 and 42
Biological: Modified E. coli heat labile enterotoxin LTR192G
Other Name: LTR192G
Experimental: Group B-1
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
Biological: Recombinant fimbrial adhesin dscCfaE
Other Name: dscCfaE
Biological: Modified E. coli heat labile enterotoxin LTR192G
Other Name: LTR192G
Experimental: Group B-2
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
Biological: Recombinant fimbrial adhesin dsc14CfaE-sCTA2/LTB5
Other Name: Chimera
Biological: Modified E. coli heat labile enterotoxin LTR192G
Other Name: LTR192G
Experimental: Group C-1
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
Biological: Recombinant fimbrial adhesin dscCfaE
Other Name: dscCfaE
Biological: Modified E. coli heat labile enterotoxin LTR192G
Other Name: LTR192G
Experimental: Group C-2
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
Biological: Recombinant fimbrial adhesin dsc14CfaE-sCTA2/LTB5
Other Name: Chimera
Biological: Modified E. coli heat labile enterotoxin LTR192G
Other Name: LTR192G
Experimental: Group D-1
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
Biological: Recombinant fimbrial adhesin dscCfaE
Other Name: dscCfaE
Biological: Modified E. coli heat labile enterotoxin LTR192G
Other Name: LTR192G
Experimental: Group D-2
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
Biological: Recombinant fimbrial adhesin dscCfaE
Other Name: dscCfaE
Biological: Modified E. coli heat labile enterotoxin LTR192G
Other Name: LTR192G

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

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01644565

Locations
United States, Maryland
Walter Reed Army Institute of Research Clinical trial Center
Silver Spring, Maryland, United States, 20910
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
Investigators
Principal Investigator: Ramiro L. Gutierrez, MD, MPH Enteric Diseases Department, Naval Medical Research Center
  More Information

Additional Information:
No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01644565     History of Changes
Other Study ID Numbers: A-17436, S-12-07, NMRC.2012.0005, 1924
Study First Received: July 11, 2012
Last Updated: July 8, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Escherichia coli Infections
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on September 18, 2014