Clinical Trial: Safety Study of Recombinant Vaccine to Prevent ETEC Diarrhea

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary: 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.
Sponsor: U.S. Army Medical Research and Materiel Command

Current Primary Outcome: Number of adverse events [ Time Frame: Days 0 - 180 ]

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


Original Primary Outcome: Safety as measured by the presence and severity of local and systemic adverse events following receipt of the investigational products. [ Time Frame: Study Days 0 - 180 ]

Current Secondary Outcome:

  • 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 ]
  • 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 ]
  • 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 ]
    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


Original Secondary Outcome: 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. [ Time Frame: Study Days 0 - 180 ]

Information By: U.S. Army Medical Research and Materiel Command

Dates:
Date Received: June 23, 2011
Date Started: July 2011
Date Completion:
Last Updated: April 24, 2015
Last Verified: April 2015