Safety Study of Recombinant Vaccine to Prevent ETEC Diarrhea

A Phase 1 Dose-Escalating Study of dscCfaE, Co-Administered With and Without LTR192G, by Transcutaneous Immunization (TCI) in Healthy Adult U.S. Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Escherichia Coli Infection
• Intervention / Treatment: Biological: Recombinant fimbrial adhesin dscCfaE; Biological: Recombinant fimbrial adhesin dscCfaE; Biological: Recombinant fimbrial adhesin dscCfaE; Biological: Modified E. coli heat labile enterotoxin 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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Walter Reed Army Institute of Research Clinical Trial Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A	Biological: Recombinant fimbrial adhesin dscCfaE; 10 ug on study days 0, 21 and 42; Other Names: dscCfaE; Biological: Recombinant fimbrial adhesin dscCfaE; 50 ug on study days 0, 21 and 42; Other Names: dscCfaE; Biological: Recombinant fimbrial adhesin dscCfaE; 250 ug on study days 0, 21 and 42; Other Names: dscCfaE; Biological: Modified E. coli heat labile enterotoxin LTR192G; 50 ug on study days 0, 21 and 42; Other Names: LTR192G
EXPERIMENTAL: Group C	Biological: Recombinant fimbrial adhesin dscCfaE; 10 ug on study days 0, 21 and 42; Other Names: dscCfaE; Biological: Recombinant fimbrial adhesin dscCfaE; 50 ug on study days 0, 21 and 42; Other Names: dscCfaE; Biological: Recombinant fimbrial adhesin dscCfaE; 250 ug on study days 0, 21 and 42; Other Names: dscCfaE; Biological: Modified E. coli heat labile enterotoxin LTR192G; 50 ug on study days 0, 21 and 42; Other Names: LTR192G
EXPERIMENTAL: Group B-1	Biological: Recombinant fimbrial adhesin dscCfaE; 10 ug on study days 0, 21 and 42; Other Names: dscCfaE; Biological: Recombinant fimbrial adhesin dscCfaE; 50 ug on study days 0, 21 and 42; Other Names: dscCfaE; Biological: Recombinant fimbrial adhesin dscCfaE; 250 ug on study days 0, 21 and 42; Other Names: dscCfaE; Biological: Modified E. coli heat labile enterotoxin LTR192G; 50 ug on study days 0, 21 and 42; Other Names: LTR192G
EXPERIMENTAL: Group B-2	Biological: Recombinant fimbrial adhesin dscCfaE; 10 ug on study days 0, 21 and 42; Other Names: dscCfaE; Biological: Recombinant fimbrial adhesin dscCfaE; 50 ug on study days 0, 21 and 42; Other Names: dscCfaE; Biological: Recombinant fimbrial adhesin dscCfaE; 250 ug on study days 0, 21 and 42; Other Names: dscCfaE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events	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	Days 0 - 180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroconversion to LT and dscCfaE; defined as a > 4-fold increase in endpoint titer between pre-and post-vaccination samples.		Study Days 0 - 180
Number of Mucosal responses (fecal IgA); defined as a > 4-fold increase in endpoint titer after adjusting for total IgA.		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	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	Study Days 0 - 180

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Investigators: Principal Investigator: Mark S. Riddle, MD, DrPH, Naval Medical Research Center

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): April 1, 2013

Study Registration Dates

• First Submitted: June 23, 2011
• First Submitted That Met QC Criteria: June 24, 2011
• First Posted (ESTIMATE): June 27, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): April 27, 2015
• Last Update Submitted That Met QC Criteria: April 24, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Diarrhea; Vaccine; ETEC
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Escherichia coli Infections
• Other Study ID Numbers: A-16682; NMRC.2011.0004 (OTHER: Naval Medical Research Center); WRAIR 1804 (OTHER: Walter Reed Army Institute of Research)