Enterotoxigenic Escherichia Coli (ETEC) ETVAX Vaccine Trial in Bangladesh
Enterotoxigenic Escherichia Coli (ETEC) ETVAX Vaccine Trial in Bangladesh
The purpose of this study is to determine if the ETEC vaccine ETVAX with and without dmLT
 adjuvant is safe and immunogenic in adults, children, toddlers and infants in Bangladesh.
This Phase I/II trial will serve to assess whether ETVAX is safe and provides mucosal as well
 as systemic immune responses against the key protective antigens when tested in different
 age-groups in Bangladesh. This study provides an opportunity to test the safety profile of a
 mucosal adjuvant, double-mutant LT (dmLT), in adults and children, as well as provide the
 opportunity to potentially assess the ability of dmLT to further enhance the mucosal and
 systemic antibody responses to key antigens in the ETVAX vaccine among age groups in
 developing country sites, like Bangladesh, that have proved refractory to oral immunization
 with enteric vaccines. In addition, this study also allows for the evaluation of the
 potential dose-sparing effect of dmLT when combined with a lower dose of vaccine. Finally,
 this clinical trial is considered an essential study along the critical path of the overall
 clinical development plan before determining whether the vaccine can be tested for protective
 efficacy in children in developing countries.
Adults

 Inclusion Criteria:

 1. Healthy male or female adults 18-45 years old, inclusive

 2. General good health as determined by the screening evaluation no greater than 7days
 before enrollment and vaccination

 3. Properly informed about the study, able to understand it and sign or thumb print the
 informed consent form

 4. Available for the entire period of the study and reachable by study staff throughout
 the entire follow-up period

 5. Females of childbearing potential who are willing to take a urine pregnancy test at
 screening and before the second vaccination. Pregnancy tests must be negative before
 each vaccination. Females of childbearing potential must agree to use an efficacious
 hormonal or barrier method of birth control during the study. Abstinence is also
 acceptable.

 6. Informed Consent (signature or thumb print provided, with witness signature)

 Exclusion Criteria:

 1. Presence of any significant known systemic disorder (cardiovascular, pulmonary,
 hepatic, renal, gastrointestinal, endocrine, immunological, dermatological,
 neurological, cancer or autoimmune disease) as determined by medical history and/or
 physical examination which would endanger the participant's health or is likely to
 result in non-conformance to the protocol.

 2. History of congenital abdominal disorders, intussusception, abdominal surgery or any
 other congenital disorder or presence of a significant medical condition that in the
 opinion of the Investigator precludes participation in the study. Known or suspected
 impairment of immunological function based on medical history and physical
 examination. Clinical evidence of active gastrointestinal illness and acute disease at
 the time of enrollment

 3. Screening positive with hepatitis B antigen and/or hepatitis C antibodies

 4. Participation in research involving another investigational product (defined as
 receipt of investigational product) during the 30 days before planned date of first
 vaccination or concurrently participating in another clinical study at any time during
 the study period, in which the participant has been or will be exposed to an
 investigational or a non-investigational product

 5. Clinically significant abnormalities in screening hematology or serum chemistry, as
 determined by the Study Physician

 6. History of febrile illness within 48 hours prior to vaccination and fever at the time
 of immunization (fever is defined as a temperature ≥ 37.5 C (99.5 F) on axillary,
 oral, or tympanic measurement)

 7. Prior receipt of any cholera (e.g., Dukoral, Shanchol) or ETEC vaccine

 8. Prior receipt of a blood transfusion or blood products, including immunoglobulins

 9. Evidence of current illicit drug use or drug dependence

 10. Current use of iron or zinc supplements within the past 7 days; current use of
 antacids (H2 blockers, omeprazole, over-the-counter (OTC) agents) or immunosuppressive
 drug

 11. Any condition which, in the opinion of the investigator, might jeopardize the safety
 of study participants or interfere with the evaluation of the study objectives

 12. Receipt of antimicrobial drugs for any reason within 14 days before vaccination

 13. History of diarrhea during the 7 days before vaccination (see protocol definition of
 diarrhea)

 14. Culture positive for ETEC, Shigella, V. Cholerae or Salmonella within 7 days before
 vaccination.

 15. Acute disease at the time of enrollment or 3 days prior to enrollment

 16. History of chronic administration (defined as more than 14 days) of immunosuppressant
 medications, including corticosteroids.

 Children, Toddlers and Infants Inclusion Criteria

 1. Healthy male or female infants/toddlers/children ages:

 -  Part B: >24 and ≤59 months old at the time of enrollment

 -  Part C: ≥12 and <24 months old at the time of enrollment

 -  Part D: ≥6 and <12 months at the time of enrollment

 2. General good health as determined by the screening evaluation no greater than 7 days
 before enrollment and vaccination

 3. Parent properly informed about the study, able to understand it and sign or thumb
 print the informed consent form

 4. Parent and child available for the entire study period of the study and reachable by
 study staff throughout the entire follow-up period

 5. Informed Consent (signature or thumb of parent, with signature of witness, provided)

 Exclusion Criteria

 1. Presence of any significant known systemic disorder (cardiovascular, pulmonary,
 hepatic, renal, gastrointestinal, endocrine, immunological, dermatological,
 neurological, cancer or autoimmune disease) as determined by medical history and/or
 physical examination which would endanger the participant's health or is likely to
 result in non-conformance to the protocol.

 2. History of congenital abdominal disorders, intussusception, abdominal surgery or any
 other congenital disorder or presence of a significant medical condition that in the
 opinion of the Investigator precludes participation in the study. Known or suspected
 impairment of immunological function based on medical history and physical
 examination. Clinical evidence of active gastrointestinal illness and acute disease at
 the time of enrollment

 3. Screening positive with hepatitis B antigen and/or hepatitis C antibodies

 4. Participation in research involving another investigational product (defined as
 receipt of investigational product) during the 30 days before planned date of first
 vaccination or concurrently participating in another clinical study at any time during
 the study period, in which the participant has been or will be exposed to an
 investigational or a non-investigational product

 5. Clinically significant abnormalities in screening hematology or serum chemistry, as
 determined by the Study Physician

 6. History of febrile illness within 48 hours prior to vaccination and fever at the time
 of immunization (fever is defined as a temperature ≥ 37.5 C (99.5 F) on axillary,
 oral, or tympanic measurement)

 7. Prior receipt of any cholera (e.g., Dukoral, Shanchol) or ETEC vaccine

 8. Prior receipt of a blood transfusion or blood products, including immunoglobulins

 9. Current use of iron or zinc supplements within the past 7 days; current use of
 antacids (H2 blockers, omeprazole, OTC agents) or immunosuppressive drug

 10. Any condition which, in the opinion of the investigator, might jeopardize the safety
 of study participants or interfere with the evaluation of the study objectives

 11. Receipt of antimicrobial drugs for any reason within 14 days before vaccination

 12. History of diarrhea during the 7 days before vaccination (see Protocol definition of
 diarrhea))

 13. Culture positive for ETEC, Shigella, V. cholerae, Salmonella or Rotavirus (the latter
 for all children <5 years of age) within 7 days of vaccination

 14. Acute disease at the time of enrollment or 3 days prior to enrollment

 15. Known or suspected impairment of immunological function based on medical history and
 physical examination

 16. Participant's parents/guardians not able, available or willing to accept active weekly
 follow-up by the study staff

 17. History of chronic administration (defined as more than 14 days) of immunosuppressant
 medications, including corticosteroids. Infants on inhaled or topical steroids may be
 permitted to participate in the study

 18. Any medical condition in the child/infant that, in the judgment of the investigator,
 would interfere with or serves as a contraindication to protocol adherence or a
 participant's parents' ability to give informed consent

 19. Medically significant malnutrition, defined as moderate malnutrition (wt-for-ht
 z-score between -3.0 and -2.0) and severe malnutrition (wt-for-ht z-score <-3.0 or
 edema)