Enterotoxigenic Escherichia Coli (ETEC) ETVAX Vaccine Trial in Bangladesh (ETVAX/dmLT)

A Randomized, Double-blind, Placebo-controlled, Dose-Escalation Study Evaluating the Safety, Tolerability, and Immunogenicity of an Oral Inactivated ETEC Vaccine (ETVAX) Alone and Together With dmLT Adjuvant in Descending Age Groups 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.

Study Overview

• Status: Completed
• Conditions: Escherichia Coli Diarrhea
• Intervention / Treatment: Biological: ETVAX; Other: Bicarbonate Buffer; Biological: dmLT

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 475
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh, 1212
    • International Centre for Diarrheal Disease, Bangladesh (icddr,b)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

21

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adult: ETVAX (Full); Adult arm (18-45 year olds) receiving the full dose of ETVAX vaccine (10^11 inactivated E. coli bacteria) added to bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water
Experimental: Adult: ETVAX (Full) + 10 ug dmLT; Adult arm (18-45 year olds) receiving the full dose of ETVAX vaccine (10^11 inactivated E. coli bacteria) with 10 ug dmLT added to bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water; Biological: dmLT; Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.; Other Names: double mutant heat labile toxin, LT(R192G/L211A)
Placebo Comparator: Adult: Placebo; Adult arm (18-45 year olds) receiving a placebo on days 0 and 14	Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water
Experimental: 24-59 months: ETVAX (1/4); 24-59 month old children receiving a quarter adult dose (2.5 x 10^10 inactivated E. coli bacteria) of ETVAX vaccine in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water
Experimental: 24-59 months: ETVAX (1/2); 24-59 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water
Experimental: 24-59 months: ETVAX (full); 24-59 month old children receiving a full adult dose of ETVAX vaccine (10^11 inactivated E. coli bacteria) in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water
Experimental: 24-59 months: ETVAX (1/2) + 2.5 ug dmLT; 24-59 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) plus 2.5 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water; Biological: dmLT; Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.; Other Names: double mutant heat labile toxin, LT(R192G/L211A)
Experimental: 24-59 months: ETVAX (1/2) + 5 ug dmLT; 24-59 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) plus 5 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water; Biological: dmLT; Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.; Other Names: double mutant heat labile toxin, LT(R192G/L211A)
Experimental: 24-59 months: ETVAX (1/2) + 10 ug dmLT; 24-59 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) plus 10 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water; Biological: dmLT; Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.; Other Names: double mutant heat labile toxin, LT(R192G/L211A)
Placebo Comparator: 24-59 months: Placebo; 24-59 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14	Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water
Experimental: 12-23 months: ETVAX (1/4); 12-23 month old children receiving a quarter adult dose of ETVAX vaccine (2.5 x 10^10 inactivated E. coli bacteria) in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water
Experimental: 12-23 months: ETVAX (1/2); 12-23 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water
Experimental: 12-23 months: ETVAX (1/2) + 2.5 ug dmLT; 12-23 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) plus 2.5 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water; Biological: dmLT; Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.; Other Names: double mutant heat labile toxin, LT(R192G/L211A)
Experimental: 12-23 months: ETVAX (1/2) + 5 ug dmLT; 12-23 month old children receiving a half adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) plus 5 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water; Biological: dmLT; Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.; Other Names: double mutant heat labile toxin, LT(R192G/L211A)
Placebo Comparator: 12-23 months: Placebo; 12-23 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14	Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water
Experimental: 6-11 months: ETVAX (1/8); 6-11 month old children receiving an eighth of an adult dose of ETVAX vaccine in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water
Experimental: 6-11 months: ETVAX (1/4); 6-11 month old children receiving a quarter of an adult dose of ETVAX vaccine (2.5 x 10^10 inactivated E. coli bacteria) in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water
Experimental: 6-11 months: ETVAX (1/2); 6-11 month old children receiving a half of an adult dose of ETVAX vaccine (5 x 10^10 inactivated E. coli bacteria) in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water
Experimental: 6-11 months: ETVAX (1/4) + 2.5 ug dmLT; 6-11 month old children receiving a quarter of an adult dose of ETVAX vaccine (2.5 x 10^10 inactivated E. coli bacteria) plus 2.5 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water; Biological: dmLT; Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.; Other Names: double mutant heat labile toxin, LT(R192G/L211A)
Experimental: 6-11 month olds: ETVAX (1/4) + 5 ug dmLT; 6-11 month old children receiving a quarter of an adult dose of ETVAX vaccine (2.5 x 10^10 inactivated E. coli bacteria) plus 5 ug dmLT in bicarbonate buffer solution administered orally on Day 0 and 14	Biological: ETVAX; Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg; E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I); E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3); E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5); E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.; Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water; Biological: dmLT; Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.; Other Names: double mutant heat labile toxin, LT(R192G/L211A)
Placebo Comparator: 6-11 month olds: Placebo; 6-11 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14	Other: Bicarbonate Buffer; Sodium bicarbonate buffer dissolved in 150 ml of potable water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Percentage of Participants Experiencing Solicited Events by Symptom and Maximum Severity	Adverse events (AEs) were assessed post-vaccination using participant/parent/guardian interview (including memory aids), targeted physical examinations, vital signs and clinical laboratory tests and reactogenicity assessments which were completed following each vaccination. The solicited AEs of nausea (adults only), abdominal pain/stomach ache (adults and children 24-59 months only), fever, vomiting and diarrhea were evaluated daily for 7 days post vaccination.	7 days after each vaccination (Day 7 and Day 21)
Number and Percentage of Participants Experiencing Unsolicited Adverse Events Related to Vaccine	Adverse events (AEs) were assessed post-vaccination using participant/parent/guardian interview (including memory aids), targeted physical examinations, vital signs and clinical laboratory tests and reactogenicity assessments which were completed following each vaccination. Unsolicited AEs were assessed through Day 42 and serious adverse events (SAEs) were assessed over the entire duration of the study.	6 months ± 14 days after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Percentage of Subjects With ≥Two-fold Increase in Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen	Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	19 days
Number and Percentage of Subjects With ≥Four-fold Increase in Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen	Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	19 days
Geometric Mean Titer (GMT) of Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen	Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	19 days
Geometric Mean Fold Change of Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen	Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	19 days
Number and Percentage of 6-11 Month Old Subjects With ≥Two-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response, by Antigen	Fecal secretion was measured on Day 7, Day 19, and Day 28; number in table is subjects experiencing a two-fold rise at any of these time points. Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	28 days
Number and Percentage of 6-11 Month Old Subjects With ≥Four-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response, by Antigen	Fecal secretion was measured on Day 7, Day 19, and Day 28; number in table is subjects experiencing a four-fold rise at any of these time points. Antigens in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	28 days
Geometric Mean Titer (GMT) of Fecal Secretory Immunoglobulin A (SIgA) Response 6-11 Month Old Subjects, by Antigen	Fecal secretion was measured on Day 7, Day 19, and Day 28; number in table is based on the maximum value for each subject. Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	28 days
Geometric Mean Fold Change of Fecal Secretory Immunoglobulin A (SIgA) Response Among 6-11 Month Old Subjects, by Antigen	Fecal secretion was measured on Day 7, Day 19, and Day 28; number in table is based on the maximum value for each subject. Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	28 days
Number and Percentage of Subjects With ≥Two-fold Increase in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for Antigens in ETVAX	Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	19 days
Number and Percentage of Subjects With ≥Four-fold Increase in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for Antigens in ETVAX	Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	19 days
Geometric Mean Titer (GMT) of Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for Antigens in ETVAX	Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	19 days
Geometric Mean Fold Change in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for Antigens in ETVAX	Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	19 days
Number and Percentage of Adult Subjects With ≥Two-fold and ≥Four-fold Increase in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for O78 Antigen	Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second).	19 days
Geometric Mean Titer (GMT) for Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for O78 Antigen, Among Adults	Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second).	19 days
Geometric Mean Fold Change in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for O78 Antigen, Among Adults	Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second).	19 days
Number and Percentage of Subjects With ≥Two-fold and ≥Four-fold Increase in Plasma Immunoglobulin G (IgG) Response to E. Coli Heat-labile Enterotoxin (LTB) After Either Vaccine Dose	Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). B-subunit of the E. coli heat-labile enterotoxin (LTB) was one of the antigens in the ETVAX vaccine.	19 days
Geometric Mean Titer (GMT) of Plasma Immunoglobulin G (IgG) Response to E. Coli Heat-labile Enterotoxin (LTB) After Either Vaccine Dose	Measured 7 days after the first dose and 5 days after the second). B-subunit of the E. coli heat-labile enterotoxin (LTB) was one of the antigens in the ETVAX vaccine.	19 days
Geometric Mean Fold Change of Plasma Immunoglobulin G (IgG) Response to E. Coli Heat-labile Enterotoxin (LTB) After Either Vaccine Dose	Between baseline and after vaccination (measured 7 days after the first dose and 5 days after the second). B-subunit of the E. coli heat-labile enterotoxin (LTB) was one of the antigens in the ETVAX vaccine.	19 days
Number of Antigen Responses in Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Experienced by Subjects		19 days
Number of Antigen Responses in Plasma Immunoglobulin A (IgA) Experienced by Subjects		19 days
Number and Percentage of 6-11 Month Old Subjects With ≥Two-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response on Day 7, by Antigen	Fecal secretion was measured on Day 0 and Day 7 (7 days after administration of first dose of vaccine). Antigens in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	7 days
Number and Percentage of 6-11 Month Old Subjects With ≥Four-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response on Day 7, by Antigen	Fecal secretion was measured on Day 0 and Day 7 (7 days after administration of first dose of vaccine). Antigens in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	7 days
Geometric Mean Titer (GMT) of Fecal Secretory Immunoglobulin A (SIgA) Response 6-11 Month Old Subjects on Day 7, by Antigen	Fecal secretion was measured on Day 7 (7 days after administration of first dose of vaccine). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	7 days
Geometric Mean Fold Change of Fecal Secretory Immunoglobulin A (SIgA) Response Among 6-11 Month Old Subjects on Day 7, by Antigen	Fecal secretion was measured on Day 0 and Day 7 (7 days after administration of first dose of vaccine). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	7 days
Number and Percentage of 6-11 Month Old Subjects With ≥Two-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response on Day 19, by Antigen	Fecal secretion was measured on Day 0 and Day 19 (5 days after administration of second dose of vaccine). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	Day 19
Number and Percentage of 6-11 Month Old Subjects With ≥Four-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response on Day 19, by Antigen	Fecal secretion was measured on Day 0 and Day 19 (5 days after administration of second dose of vaccine). Antigens in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	19 days
Geometric Mean Titer (GMT) of Fecal Secretory Immunoglobulin A (SIgA) Response 6-11 Month Old Subjects on Day 19, by Antigen	Fecal secretion was measured on Day 19 (5 days after administration of second dose of vaccine). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	19 days
Geometric Mean Fold Change of Fecal Secretory Immunoglobulin A (SIgA) Response Among 6-11 Month Old Subjects on Day 19, by Antigen	Fecal secretion was measured on Day 0 and Day 19 (5 days after administration of second dose of vaccine). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	19 days
Number and Percentage of 6-11 Month Old Subjects With ≥Two-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response on Day 28, by Antigen	Fecal secretion was measured on Day 0 and Day 28 (2 weeks after administration of second dose of vaccine). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	28 days
Number and Percentage of 6-11 Month Old Subjects With ≥Four-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response on Day 28, by Antigen	Fecal secretion was measured on Day 0 and Day 28 (2 weeks after administration of second dose of vaccine). Antigens in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	28 days
Geometric Mean Titer (GMT) of Fecal Secretory Immunoglobulin A (SIgA) Response 6-11 Month Old Subjects on Day 28, by Antigen	Fecal secretion was measured on Day 28 (2 weeks after administration of second dose of vaccine). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	28 days
Geometric Mean Fold Change of Fecal Secretory Immunoglobulin A (SIgA) Response Among 6-11 Month Old Subjects on Day 28, by Antigen	Fecal secretion was measured on Day 0 and Day 28 (2 weeks after administration of second dose of vaccine). Antigen in ETVAX were: E. coli, CFA/I, strain ETEX 21 formalin inactivated, E. coli, CS3, strain ETEX 22 formalin inactivated, E. coli, CS5, strain ETEX 23 formalin inactivated, E. coli, CS6, strain ETEX 24 phenol inactivated, B-subunit of the E. coli heat-labile enterotoxin	28 days

Collaborators and Investigators

• Sponsor: PATH
• Collaborators: International Centre for Diarrhoeal Disease Research, Bangladesh; Scandinavian Biopharma AB

Publications and helpful links

General Publications

• Higginson EE, Sayeed MA, Pereira Dias J, Shetty V, Ballal M, Srivastava SK, Willis I, Qadri F, Dougan G, Mutreja A. Microbiome Profiling of Enterotoxigenic Escherichia coli (ETEC) Carriers Highlights Signature Differences between Symptomatic and Asymptomatic Individuals. mBio. 2022 Jun 28;13(3):e0015722. doi: 10.1128/mbio.00157-22. Epub 2022 May 10.
• Qadri F, Akhtar M, Bhuiyan TR, Chowdhury MI, Ahmed T, Rafique TA, Khan A, Rahman SIA, Khanam F, Lundgren A, Wiklund G, Kaim J, Lofstrand M, Carlin N, Bourgeois AL, Maier N, Fix A, Wierzba T, Walker RI, Svennerholm AM. Safety and immunogenicity of the oral, inactivated, enterotoxigenic Escherichia coli vaccine ETVAX in Bangladeshi children and infants: a double-blind, randomised, placebo-controlled phase 1/2 trial. Lancet Infect Dis. 2020 Feb;20(2):208-219. doi: 10.1016/S1473-3099(19)30571-7. Epub 2019 Nov 19.
• Akhtar M, Chowdhury MI, Bhuiyan TR, Kaim J, Ahmed T, Rafique TA, Khan A, Rahman SIA, Khanam F, Begum YA, Sharif MZ, Islam LN, Carlin N, Maier N, Fix A, Wierzba TF, Walker RI, Bourgeois AL, Svennerholm AM, Qadri F, Lundgren A. Evaluation of the safety and immunogenicity of the oral inactivated multivalent enterotoxigenic Escherichia coli vaccine ETVAX in Bangladeshi adults in a double-blind, randomized, placebo-controlled Phase I trial using electrochemiluminescence and ELISA assays for immunogenicity analyses. Vaccine. 2019 Sep 3;37(37):5645-5656. doi: 10.1016/j.vaccine.2018.11.040. Epub 2018 Nov 22.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): July 29, 2017
• Study Completion (Actual): July 29, 2017

Study Registration Dates

• First Submitted: August 17, 2015
• First Submitted That Met QC Criteria: August 20, 2015
• First Posted (Estimate): August 24, 2015

Study Record Updates

• Last Update Posted (Actual): September 12, 2018
• Last Update Submitted That Met QC Criteria: September 10, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: ETEC diarrhea; Escherichia Coli (ETEC)
• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Diarrhea; Escherichia coli Infections
• Other Study ID Numbers: VAC 014