Enterotoxigenic Escherichia Coli (ETEC) ETVAX Vaccine Trial in Bangladesh

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02531802
• Date of registration: 17/08/2015
• Prospective Registration: Yes
• Primary sponsor: PATH
• Public title: Enterotoxigenic Escherichia Coli (ETEC) ETVAX Vaccine Trial in Bangladesh ETVAX/dmLT
• Scientific title: 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
• Date of first enrolment: October 2015
• Target sample size: 475
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02531802
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

Bangladesh

Key inclusion & exclusion criteria

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 parti


Age minimum: 6 Months
Age maximum: 45 Years
Gender: All

Health Condition(s) or Problem(s) studied

Escherichia Coli Diarrhea

Intervention(s)

Biological: dmLT

Other: Bicarbonate Buffer

Biological: ETVAX

Primary Outcome(s)

Number and Percentage of Participants Experiencing Unsolicited Adverse Events Related to Vaccine [Time Frame: 6 months ± 14 days after the first dose]

Number and Percentage of Participants Experiencing Solicited Events by Symptom and Maximum Severity [Time Frame: 7 days after each vaccination (Day 7 and Day 21)]

Secondary Outcome(s)

Geometric Mean Fold Change of Fecal Secretory Immunoglobulin A (SIgA) Response Among 6-11 Month Old Subjects on Day 28, by Antigen [Time Frame: 28 days]

Geometric Mean Titer (GMT) of Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen [Time Frame: 19 days]

Geometric Mean Titer (GMT) of Fecal Secretory Immunoglobulin A (SIgA) Response 6-11 Month Old Subjects on Day 7, by Antigen [Time Frame: 7 days]

Geometric Mean Titer (GMT) of Plasma Immunoglobulin G (IgG) Response to E. Coli Heat-labile Enterotoxin (LTB) After Either Vaccine Dose [Time Frame: 19 days]

Number and Percentage of 6-11 Month Old Subjects With =Four-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response, by Antigen [Time Frame: 28 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 [Time Frame: 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 [Time Frame: 19 days]

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 [Time Frame: 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 [Time Frame: 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 [Time Frame: 19 days]

Geometric Mean Fold Change in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for O78 Antigen, Among Adults [Time Frame: 19 days]

Geometric Mean Fold Change in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for Antigens in ETVAX [Time Frame: 19 days]

Geometric Mean Titer (GMT) of Fecal Secretory Immunoglobulin A (SIgA) Response 6-11 Month Old Subjects on Day 28, by Antigen [Time Frame: 28 days]

Geometric Mean Fold Change of Fecal Secretory Immunoglobulin A (SIgA) Response Among 6-11 Month Old Subjects on Day 7, by Antigen [Time Frame: 7 days]

Geometric Mean Fold Change of Fecal Secretory Immunoglobulin A (SIgA) Response Among 6-11 Month Old Subjects, by Antigen [Time Frame: 28 days]

Number of Antigen Responses in Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Experienced by Subjects [Time Frame: 19 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 [Time Frame: 7 days]

Geometric Mean Fold Change of Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen [Time Frame: 19 days]

Geometric Mean Titer (GMT) of Fecal Secretory Immunoglobulin A (SIgA) Response 6-11 Month Old Subjects on Day 19, by Antigen [Time Frame: 19 days]

Geometric Mean Fold Change of Plasma Immunoglobulin G (IgG) Response to E. Coli Heat-labile Enterotoxin (LTB) After Either Vaccine Dose [Time Frame: 19 days]

Geometric Mean Titer (GMT) for Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for O78 Antigen, Among Adults [Time Frame: 19 days]

Number and Percentage of 6-11 Month Old Subjects With =Two-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response, by Antigen [Time Frame: 28 days]

Geometric Mean Titer (GMT) of Fecal Secretory Immunoglobulin A (SIgA) Response 6-11 Month Old Subjects, by Antigen [Time Frame: 28 days]

Geometric Mean Titer (GMT) of Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for Antigens in ETVAX [Time Frame: 19 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 [Time Frame: 28 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 [Time Frame: Day 19]

Number and Percentage of Subjects With =Four-fold Increase in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for Antigens in ETVAX [Time Frame: 19 days]

Number of Antigen Responses in Plasma Immunoglobulin A (IgA) Experienced by Subjects [Time Frame: 19 days]

Geometric Mean Fold Change of Fecal Secretory Immunoglobulin A (SIgA) Response Among 6-11 Month Old Subjects on Day 19, by Antigen [Time Frame: 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 [Time Frame: 7 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 [Time Frame: 19 days]

Number and Percentage of Subjects With =Two-fold Increase in Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen [Time Frame: 19 days]

Secondary ID(s)

VAC 014

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

International Centre for Diarrhoeal Disease Research, Bangladesh

Scandinavian Biopharma AB

Results

• Results available: Yes
• Date Posted: 12/09/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02531802