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
1 other identifier
interventional
475
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2015
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 17, 2015
CompletedFirst Posted
Study publicly available on registry
August 24, 2015
CompletedStudy Start
First participant enrolled
October 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 29, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
July 29, 2017
CompletedResults Posted
Study results publicly available
September 12, 2018
CompletedSeptember 12, 2018
September 1, 2018
1.8 years
August 17, 2015
August 3, 2018
September 10, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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 Outcomes (32)
Number and Percentage of Subjects With ≥Two-fold Increase in Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen
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
19 days
Geometric Mean Titer (GMT) of Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen
19 days
Geometric Mean Fold Change of Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response After Either Vaccine Dose, by Antigen
19 days
Number and Percentage of 6-11 Month Old Subjects With ≥Two-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response, by Antigen
28 days
- +27 more secondary outcomes
Study Arms (21)
Adult: ETVAX (Full)
EXPERIMENTALAdult 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
Adult: ETVAX (Full) + 10 ug dmLT
EXPERIMENTALAdult 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
Adult: Placebo
PLACEBO COMPARATORAdult arm (18-45 year olds) receiving a placebo on days 0 and 14
24-59 months: ETVAX (1/4)
EXPERIMENTAL24-59 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
24-59 months: ETVAX (1/2)
EXPERIMENTAL24-59 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
24-59 months: ETVAX (full)
EXPERIMENTAL24-59 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
24-59 months: ETVAX (1/2) + 2.5 ug dmLT
EXPERIMENTAL24-59 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
24-59 months: ETVAX (1/2) + 5 ug dmLT
EXPERIMENTAL24-59 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
24-59 months: ETVAX (1/2) + 10 ug dmLT
EXPERIMENTAL24-59 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
24-59 months: Placebo
PLACEBO COMPARATOR24-59 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14
12-23 months: ETVAX (1/4)
EXPERIMENTAL12-23 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
12-23 months: ETVAX (1/2)
EXPERIMENTAL12-23 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
12-23 months: ETVAX (1/2) + 2.5 ug dmLT
EXPERIMENTAL12-23 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
12-23 months: ETVAX (1/2) + 5 ug dmLT
EXPERIMENTAL12-23 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
12-23 months: Placebo
PLACEBO COMPARATOR12-23 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14
6-11 months: ETVAX (1/8)
EXPERIMENTAL6-11 month old children receiving an eighth of an adult dose of ETVAX vaccine in bicarbonate buffer solution administered orally on Day 0 and 14
6-11 months: ETVAX (1/4)
EXPERIMENTAL6-11 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
6-11 months: ETVAX (1/2)
EXPERIMENTAL6-11 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
6-11 months: ETVAX (1/4) + 2.5 ug dmLT
EXPERIMENTAL6-11 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
6-11 month olds: ETVAX (1/4) + 5 ug dmLT
EXPERIMENTAL6-11 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
6-11 month olds: Placebo
PLACEBO COMPARATOR6-11 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14
Interventions
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.
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.
Sodium bicarbonate buffer dissolved in 150 ml of potable water
Eligibility Criteria
You may qualify if:
- Healthy male or female adults 18-45 years old, inclusive
- General good health as determined by the screening evaluation no greater than 7days before enrollment and vaccination
- Properly informed about the study, able to understand it and sign or thumb print the informed consent form
- Available for the entire period of the study and reachable by study staff throughout the entire follow-up period
- 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.
- Informed Consent (signature or thumb print provided, with witness signature)
You may not qualify if:
- 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.
- 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
- Screening positive with hepatitis B antigen and/or hepatitis C antibodies
- 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
- Clinically significant abnormalities in screening hematology or serum chemistry, as determined by the Study Physician
- 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)
- Prior receipt of any cholera (e.g., Dukoral, Shanchol) or ETEC vaccine
- Prior receipt of a blood transfusion or blood products, including immunoglobulins
- Evidence of current illicit drug use or drug dependence
- 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
- 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
- Receipt of antimicrobial drugs for any reason within 14 days before vaccination
- History of diarrhea during the 7 days before vaccination (see protocol definition of diarrhea)
- Culture positive for ETEC, Shigella, V. Cholerae or Salmonella within 7 days before vaccination.
- Acute disease at the time of enrollment or 3 days prior to enrollment
- +28 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- PATHlead
- Scandinavian Biopharma ABcollaborator
- International Centre for Diarrhoeal Disease Research, Bangladeshcollaborator
Study Sites (1)
International Centre for Diarrheal Disease, Bangladesh (icddr,b)
Dhaka, 1212, Bangladesh
Related Publications (3)
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.
PMID: 35536001DERIVEDQadri 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.
PMID: 31757774DERIVEDAkhtar 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.
PMID: 30473185DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Jorge Flores
- Organization
- PATH
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 17, 2015
First Posted
August 24, 2015
Study Start
October 1, 2015
Primary Completion
July 29, 2017
Study Completion
July 29, 2017
Last Updated
September 12, 2018
Results First Posted
September 12, 2018
Record last verified: 2018-09