Safety Study of Recombinant Vaccine to Prevent ETEC Diarrhea

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01382095
First received: June 23, 2011
Last updated: April 24, 2015
Last verified: April 2015
  Purpose

The purpose of the study is to determine if immunization with a recombinant E. coli protein, dscCfaE, is safe and immunogenic when administered through the skin using a patch.


Condition Intervention Phase
Escherichia Coli Infection
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 Dose-Escalating Study of dscCfaE, Co-Administered With and Without LTR192G, by Transcutaneous Immunization (TCI) in Healthy Adult U.S. Volunteers

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of adverse events [ Time Frame: Days 0 - 180 ] [ Designated as safety issue: Yes ]
    Adverse event monitoring will survey and specifically inquire about fever (oral temperature > 100.4 o F), malaise, headache, rash, pain, diarrhea, abdominal pain, extremity pain or swelling. Clinical definitions will be used to grade severity of symptoms in accordance to the severity scale below: Grade 0 = None Grade 1= Barely noticeable Grade 2= Noticeable, does not interfere with daily activities Grade 3=Interferes with daily activities Grade 4=Prevents daily activities


Secondary Outcome Measures:
  • Number of Seroconversion to LT and dscCfaE; defined as a > 4-fold increase in endpoint titer between pre-and post-vaccination samples. [ Time Frame: Study Days 0 - 180 ] [ Designated as safety issue: No ]
  • Number of Mucosal responses (fecal IgA); defined as a > 4-fold increase in endpoint titer after adjusting for total IgA. [ Time Frame: Study Days 0 - 180 ] [ Designated as safety issue: No ]
  • Number of positive IgA-ASC responses; defined as a > 2-fold increase over th e baseline value of the ASC per 10 6 PBMC, when the number of ASC is > 0.5 per 10 6 in the baseline sample [ Time Frame: Study Days 0 - 180 ] [ Designated as safety issue: No ]
    A positive IgA-ASC response will be defined as a > 2-fold increase over th e baseline value of the ASC per 10 6 PBMC, when the number of ASC is > 0.5 per 10 6 in the baseline sample. When the number of baseline ASCs is less than 0.5 per 10 6 PBMC, a subject will be considered a responder if the post-vaccination value is greater than 1.0 per 10 6 PBMC


Enrollment: 40
Study Start Date: July 2011
Study Completion Date: April 2013
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A Biological: Recombinant fimbrial adhesin dscCfaE
10 ug on study days 0, 21 and 42
Other Name: dscCfaE
Biological: Modified E. coli heat labile enterotoxin LTR192G
50 ug on study days 0, 21 and 42
Other Name: LTR192G
Experimental: Group B-1 Biological: Recombinant fimbrial adhesin dscCfaE
50 ug on study days 0, 21 and 42
Other Name: dscCfaE
Biological: Modified E. coli heat labile enterotoxin LTR192G
50 ug on study days 0, 21 and 42
Other Name: LTR192G
Experimental: Group B-2 Biological: Recombinant fimbrial adhesin dscCfaE
50 ug on study days 0, 21 and 42
Other Name: dscCfaE
Experimental: Group C Biological: Recombinant fimbrial adhesin dscCfaE
250 ug on study days 0, 21 and 42
Other Name: dscCfaE
Biological: Modified E. coli heat labile enterotoxin LTR192G
50 ug on study days 0, 21 and 42
Other Name: LTR192G

Detailed Description:

The purpose of the study is to determine if immunization with dscCfaE with or without a modified E. coli heat labile enterotoxin, LTR192G, is safe and immunogenic when administered transcutaneously using a skin wet-patch. If the vaccine is found safe and adequately immunogenic in humans, a phase 2b vaccination/challenge study would be undertaken to further evaluate vaccine safety and allow a preliminary assessment of efficacy. 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 such as, chronic medical conditions such as psychiatric conditions, diabetes mellitus, hypertension or any other conditions that might place the volunteer at increased risk of adverse events. Study clinicians, in consultation with the principal investigator (PI), will use clinical judgment on a case-by-case basis to assess safety risks under this criterion. The PI will consult with the Medical Monitor as appropriate.
  • Clinically significant abnormalities on physical examination.
  • Immunosuppressive drugs (use of systemic corticosteroids or chemotherapeutics that may influence antibody development) or illness (including IgA deficiency).
  • 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.
  • Immunosuppressive illness or IgA deficiency (below the normal limits).
  • Exclusionary skin history/findings that would confound assessment or prevent appropriate local monitoring of adverse events (AEs), or possibly increase the risk of an AE.
  • History of chronic skin disease (clinician judgment).
  • History of atopy.
  • 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.
  • History of microbiologically confirmed Enterotoxigenic E. coli (ETEC) or V. cholerae infection.
  • Travel to countries where ETEC or V. cholerae 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. cholerae vaccine or live ETEC or V. cholerae challenge.
  • Occupation involving handling of ETEC or V. cholerae currently, or in the past 3 years.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01382095

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: Mark S. Riddle, MD, DrPH Naval Medical Research Center
  More Information

No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01382095     History of Changes
Other Study ID Numbers: A-16682, NMRC.2011.0004, WRAIR 1804
Study First Received: June 23, 2011
Last Updated: April 24, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:
ETEC
Diarrhea
Vaccine

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

ClinicalTrials.gov processed this record on August 27, 2015