Prevention of Diarrheal Disease Due to Infection With Enterotoxigenic E. Coli (ETEC)

NCT03729219 | Completed Phase 2

• 1 other identifier: OEV 123
• Study Type: interventional
• Target: 749
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II b, double-blind, randomized, placebo-controlled study in healthy adults (age 18-65 years) to evaluate the safety, immunogenicity, different diagnostic tools and efficacy of ETVAX. Participants will travel to Grand Popo, Africa for 12 days. Prior travelling participants will be vaccinated with two doses of vaccine or placebo. Vaccine Preventable Outcome will be identified and then characterized as to incidence, duration, severity and frequency of Moderate or Severe Travellers diarrhea. Health related information and assessments will be recorded during the travel.

Conditions

Diarrhea

Outcome Measures

Primary Outcomes (6)

• Safety: Number of vaccine attributable adverse events

  Number of vaccine attributable adverse events

  From first vaccination until leave for Benin, approximately 13-50 days

• Immunogenicity: Fold change of serum titers of IgA and IgG against LTB

  Fold change of serum titers of Immunoglobulin A (IgA) and Immunoglobulin G (IgG) against heat-labile toxin (LTB)

  Change from baseline (just before first vaccination) to Visit 3 (5-6 days after second vaccination), an average of 20 days

• Immunogenicity: Number of subjects responding to heat-labile toxin (LTB)

  Number of subjects responding to heat-labile toxin (LTB) based on serum Immunoglobulin A (IgA) and Immunoglobulin G (IgG) (i.e. fold change at least 2)

  Change from baseline (just before first vaccination) to Visit 3 (5-6 days after second vaccination), an average of 20 days

• Immunogenicity: Fold change of serum titers of Immunoglobulin A (IgA) and Immunoglobulin G (IgG) against O78 lipopolysaccharide (LPS)

  Fold change of serum titers of Immunoglobulin A (IgA) and Immunoglobulin G (IgG) against O78 lipopolysaccharide (LPS)

  Change from baseline (just before first vaccination) to Visit 3 (5-6 days after second vaccination), an average of 20 days

• Immunogenicity: Number of subjects responding to O78 lipopolysaccharide (LPS)

  Number of subjects responding to O78 lipopolysaccharide (LPS) based on serum Immunoglobulin A (IgA) and Immunoglobulin G (IgG) (i.e. fold change at least 2)

  Change from baseline (just before first vaccination) to Visit 3 (5-6 days after second vaccination), an average of 20 days

• Diagnostic Tools:To set the optimal threshold limits of the two quantitativePolymerase chain reaction (PCR ) procedures

  To set the optimal threshold limits of the two quantitative Polymerase chain reaction (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 clinically significant ETEC TD cases, as well as cases associated with other enteric pathogens using the culture based bacterial detection method as the "Gold standard" for comparison.

  12 days in Benin and 30 days post-travel in Finland, approximately 42 days

Secondary Outcomes (3)

• Efficacy: The incidence of Vaccine Preventable Outcomes (VPO)

  12 days in Benin and 30 days post-travel in Finland, approximately 42 days

• Diagnostic Tools:Extent to which the non-culture based PCR assays can help resolve mixed ETEC infections

  12 days in Benin and 30 days post-travel in Finland, approximately 42 days

• Diagnostic Tools:The extent to which the TaqMan array yields results for ETEC colonization factor that are comparable to those obtained by culture based methods.

  12 days in Benin and 30 days post-travel in Finland, approximately 42 days

Study Arms (2)

ETVAX

EXPERIMENTAL

Contains inactivated Tetravalent ETEC vaccine, 10 ug Double-mutant heat-labile toxin (dmLT) and effervescent power for oral solution administered twice 14 (plus minus 7) days intervals.

Biological: E. coli ETVAX

Placebo

PLACEBO COMPARATOR

Effervescent power for oral solution administered wice 14 (plus-minus 7) days intervals

Other: Placebo

Interventions

E. coli ETVAX BIOLOGICAL

Oral suspension Sterile water is added to dmLT . Vaccine is poured to the effervescent solution and needed amount of dmLT is added.

ETVAX

Placebo OTHER

Oral suspension

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female age ≥18 and ≤ 65 years
• General good health at the time of first vaccination
• Female participants of childbearing potential must not be pregnant
• Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study
• Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained
• Availability for the study duration, including all planned follow-up visits
• Intake of atovaquone + proguanil (Malarone) as anti-malaria prophylax according to prescription guidelines mandatory before, during and after travel to Benin

You may not qualify if:

• Presence of a significant medical or psychiatric condition, which in the opinion of the investigator precludes participation in the study
• Known or suspected history of drug, chemical or alcohol abuse, as deemed by the investigator/physician; AUDIT \> 13 points
• Known recent history of impaired immune function which, according to the judgement of the investigator could influence the immune response
• Intends to receive any other investigational vaccine during the study period, or within two weeks prior to study vaccination
• Intends to donate blood at any time during the study.
• 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
• Any history of psychosis or bipolar disorder or on-going significant mental disorder
• Regular (daily) use of laxatives or agents which lower stomach acidity (antacids, proton pump inhibitors) less than one week before visit V1
• 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
• Traveled to ETEC-endemic areas within the last year or visit for \> two months in ETEC endemic areas during the last 10 years
• Receipt of Dukoral or other ETEC or cholera vaccines within 3 years or planned receipt of such vaccine except ETVAX during the study
• Antibiotic therapy within two weeks prior to the vaccination
• History of diarrhea in the 7 days prior to vaccination (defined as ≥ 3 unformed loose stools in 24 hours)
• 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

Sponsors & Collaborators

• Scandinavian Biopharma AB: lead
• Göteborg University: collaborator
• United Medix Laboratories Ltd.: collaborator
• Oy Medfiles Ltd: collaborator
• University of Helsinki: collaborator
• University of Virginia: collaborator

Study Sites (1)

Lääkärikeskus Aava, matkailuklinikka

Helsinki, Finland

Location

Related Publications (1)

• Liu J, Jokiranta TS, Carlin N, Stroup S, Zhang J, Sjostrand B, Svennerholm A-M, Houpt ER, Kantele A. Use of a TaqMan Array Card for identification of enterotoxins and colonization factors directly from stool samples in an enterotoxigenic E. coli vaccine study. Microbiol Spectr. 2025 Mar 4;13(3):e0187024. doi: 10.1128/spectrum.01870-24. Epub 2025 Feb 11.

  PMID: 39932427 DERIVED

MeSH Terms

Conditions

Diarrhea

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Anu Kantele

  University of Helsinki, Dept. of Infectious Diseases

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Other parts will be blinded except unblinded person who prepares the doses.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A randomized, placebo-controlled phase IIb

Study Record Dates

• First Submitted: October 16, 2017
• First Posted: November 2, 2018
• Study Start: June 12, 2017
• Primary Completion: April 15, 2019
• Study Completion: April 15, 2019
• Last Updated: November 8, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)