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

July 11, 2012
July 8, 2013
August 2012
August 2013   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01644565 on ClinicalTrials.gov Archive Site
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.
Same as current
Not Provided
Not Provided
 
Safety Study of Chimeric Vaccine to Prevent ETEC Diarrhea
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

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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Escherichia Coli Infection
  • Biological: Recombinant fimbrial adhesin dsc14CfaE-sCTA2/LTB5
    Other Name: Chimera
  • Biological: Recombinant fimbrial adhesin dscCfaE
    Other Name: dscCfaE
  • Biological: Modified E. coli heat labile enterotoxin LTR192G
    Other Name: LTR192G
  • Experimental: Group A-1
    Recombinant fimbrial adhesin dscCfaE: 1 ug of dscCfaE ID on study days 0, 21 and 42
    Intervention: Biological: Recombinant fimbrial adhesin dscCfaE
  • Experimental: Group A-2
    Recombinant fimbrial adhesin dsc14CfaE-sCTA2/LTB5: 2.6 ug of Chimera ID on study days 0, 21 and 42
    Intervention: Biological: Recombinant fimbrial adhesin dsc14CfaE-sCTA2/LTB5
  • Experimental: Group A-3
    Modified E. coli heat labile enterotoxin LTR192G: 100 ng of LTR192G ID on study days 0, 21 and 42
    Intervention: Biological: Modified E. coli heat labile enterotoxin 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
    Interventions:
    • Biological: Recombinant fimbrial adhesin dscCfaE
    • Biological: Modified E. coli heat labile enterotoxin 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
    Interventions:
    • Biological: Recombinant fimbrial adhesin dsc14CfaE-sCTA2/LTB5
    • Biological: Modified E. coli heat labile enterotoxin 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
    Interventions:
    • Biological: Recombinant fimbrial adhesin dscCfaE
    • Biological: Modified E. coli heat labile enterotoxin 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
    Interventions:
    • Biological: Recombinant fimbrial adhesin dsc14CfaE-sCTA2/LTB5
    • Biological: Modified E. coli heat labile enterotoxin 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
    Interventions:
    • Biological: Recombinant fimbrial adhesin dscCfaE
    • Biological: Modified E. coli heat labile enterotoxin 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
    Interventions:
    • Biological: Recombinant fimbrial adhesin dscCfaE
    • Biological: Modified E. coli heat labile enterotoxin LTR192G
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
57
August 2013
August 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years to 45 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01644565
A-17436, S-12-07, NMRC.2012.0005, 1924
Yes
U.S. Army Medical Research and Materiel Command
U.S. Army Medical Research and Materiel Command
Not Provided
Principal Investigator: Ramiro L. Gutierrez, MD, MPH Enteric Diseases Department, Naval Medical Research Center
U.S. Army Medical Research and Materiel Command
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP