Healthy voluteers (prevention of diarrheal disease due to infection with enterotoxigenic E. coli [ETEC]) MedDRA version: 19.1 Level: LLT Classification code 10054242 Term: Escherichia coli infection System Organ Class: 100000004862 MedDRA version: 19.1 Level: LLT Classification code 10044552 Term: Traveller's diarrhea System Organ Class: 100000004862
Conditions
Interventions
Product Name: ETVAX
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Not known
Other descriptive name: ESCHERICHIA COLI (INACTIVATED)
Concentration unit: million organisms million organisms
C
Sponsors
Scandinavian Biopharma AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female age =18 and = 65 years. 2. General good health at the time of first vaccination. 3. Female participants of childbearing potential must declare that they are not pregnant. 4. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. 5. Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained. 6. Availability for the study duration, including all planned follow-up visits. 7. Intake of atovaquone+proguanil (Malarone/Rumbacor) as anti-malaria profylax according to prescription guidelines mandatory before, during and after travel to Benin. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 800 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Presence of a significant medical or psychiatric condition, which in the opinion of the investigator precludes participation in the study. 2. Known or suspected history of drug, chemical or alcohol abuse, as deemed by the investigator/physician 3. Known recent history of impaired immune function which, according to the judgement of the investigator could influence the immune response. 4. Intends to receive any other investigational vaccine during the study period, or within two weeks prior to study vaccination. 5. Intends to donate blood at any time during the study. 6. An acute or chronic medical condition that, in the opinion of the investigator/physician, would render ingestion of the investigational products unsafe or would interfere with the evaluation of responses. This includes, but is not limited to gastrointestinal diseases and autoimmune diseases requiring treatment. 7. Regular (daily) use of laxatives or agents which lower stomach acidity (antacids, proton pump inhibitors) less than one week before inclusion. 8. Use of any oral or parenteral medication known to affect the immune function (e.g., corticosteroids and others) within 30 days preceding the first vaccination or planned use during the active study period. 9. Traveled to ETEC-endemic areas within the last year or visit for > two months in ETEC endemic areas during the last 10 years. 10. Receipt of Dukoral or other ETEC or cholera vaccines within 3 years or planned receipt of such vaccine except ETVAX during the study. 11. Antibiotic therapy within two weeks prior to the vaccination. 12. History of diarrhea in the 7 days prior to vaccination (defined as = 3 unformed loose stools in 24 hours). 13. Any other criteria which, in the investigator's opinion, would compromise the ability of the traveler to participate in the study, the safety of the study, or the results of the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety: To evaluate safety and tolerability of orally administered ETVAX vaccine in a two dose regimen. Immunogenicity: To evaluate the immune response in serum against LTB and O78 LPS. Diagnostic Tools: To elucidate the agreement between culture based and non-culture based diagnostic tools for identifying ETEC and other enteric pathogens in stool samples from travelers meeting pre-defined clinical end-points for moderate or severe Traveller's Diarrhea (TD). Culture-based diagnostics are performed on bacterial colonies isolated from stool samples and analyzed by biochemical, mass-spectrometric and immunological methods, and non-culture based methods are performed on frozen bacteriological cell line samples using a validated multiplex quantitative PCR developed by Mobidiag Oy, Finland and a modified TaqMan array developed by UVA and NMRC in the US. ;Secondary Objective: Efficacy: To evaluate the protective efficacy (PE) of the vaccine against moderate or severe, culture confirmed, Vaccine Preventable Outcome (VPO) ETEC-induced diarrhea in Finnish travelers to Benin. Immunogenicity: To evaluate the relationship between serum IgA/IgG anti-LTB levels approx. one week after the second dose and the risk of developing moderate or severe ETEC TD. ;Primary end point(s): Safety: Number of vaccine attributable events. Immunogenicity: Frequencies and magnitudes of serum IgA and IgG antibody responses to LTB and/or O78 LPS following immunization. Diagnostic Tools: To set the optimal threshold limits of the two quantitative PCR procedures by setting limits for the number of amplification cycles (Cq values) which best allows (in terms of sensitivity, specificity, and positive predictive value) for identification of moderate or severe ETEC TD cases, as well as cases associated with other enteric pathogens using the culture based antigen detection methods as the “Gold-standard” for comparison.;Timepoint(s) of evaluation of this end point: Safety: Immediate Adve | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: The incidence of cases with moderate or severe ETEC VPO diarrhea in the vaccinated and placebo groups of travelers. Immunogenicity : The incidence of cases with moderate or severe ETEC VPO diarrhea in relation to the serum antibody response against LTB. Diagnostic tools: The extent to which the non-culture based PCR assays can help resolve mixed enteric infections and enable attribution to be reasonably assigned to ETEC as the causative pathogen, against more traditional culture-based or antigen detection methods. Also, the extent to which the TaqMan array yields results for ETEC colonizatiom factor that are comparable to those obtained by culture based methods.;Timepoint(s) of evaluation of this end point: Efficacy: Routine stool samples collected on day 4-7 during travel (11-37 days after second vaccination) and 1-2 days after travel (20-44 days after second vaccination). Stool samples also collected during travel in case of diarrhea episodes. Travel-questionnaire, Q2 reviewed 1-2 days after travel and travel-questinnaire Q3 reviewed 25-35 days after travel. Diarrhea reporting form (DFR) reviewed 1-2 days after travel, if applicable. Immunogenicity: Serum collected prior first vaccination, 5-6 days post second vaccination and 1-2 days after travel (20-44 days post second vaccination) for LTB, O78-specific IgA in serum. Diagnostic tools: as specified in timepoints for primary end points. | — |
Countries
Benin, Finland
Contacts
Public ContactPrincipal Investigator
Helsinki University Hospital
Outcome results
None listed