Escherichia Coli DiarrheaPhase 1/2ETVAX/dmLTNCT02531802
Enterotoxigenic Escherichia Coli (ETEC) ETVAX Vaccine Trial in Bangladesh
A Phase 1/2 study testing ETVAX, dmLT and Bicarbonate Buffer in people with Escherichia Coli Diarrhea, run by PATH at 1 site in Bangladesh.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Escherichia Coli Diarrhea
- What is being tested?
- ETVAX, dmLT and Bicarbonate Buffer
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 475 participants
- Where
- 1 siteBangladesh
- Study dates
- Oct 2015to 29 Jul 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 45 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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)
Who cannot join
- 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)
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- 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
- History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids.
- Children, Toddlers and Infants Inclusion Criteria
- 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
- General good health as determined by the screening evaluation no greater than 7 days before enrollment and vaccination
- Parent properly informed about the study, able to understand it and sign or thumb print the informed consent form
- Parent and child available for the entire study period of the study and reachable by study staff throughout the entire follow-up period
- Informed Consent (signature or thumb of parent, with signature of witness, provided)
- 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
- Current use of iron or zinc supplements within the past 7 days; current use of antacids (H2 blockers, omeprazole, 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, Salmonella or Rotavirus (the latter for all children <5 years of age) within 7 days of vaccination
- Acute disease at the time of enrollment or 3 days prior to enrollment
- Known or suspected impairment of immunological function based on medical history and physical examination
- Participant's parents/guardians not able, available or willing to accept active weekly follow-up by the study staff
- 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
- 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
- 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)
Trial locations and contacts
1 site in 1 country.
Bangladesh1 site
International Centre for Diarrheal Disease, Bangladesh (icddr,b)
Dhaka, 1212
About this study
Official 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
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.
Read the 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.
- Conditions
- Escherichia Coli Diarrhea
- Being tested
- ETVAX, dmLT, Bicarbonate Buffer
- Keywords
- ETEC diarrhea, Escherichia Coli (ETEC)
- Medical subject headings
- Escherichia coli Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ETVAXBiological
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.
dmLTBiological
Also called double mutant heat labile toxin, LT(R192G/L211A)
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.
Bicarbonate BufferOther
Sodium bicarbonate buffer dissolved in 150 ml of potable water
| Study group | Role | What they receive |
|---|---|---|
| Adult: ETVAX (Full) | Experimental | 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 Receives: Biological: ETVAX; Other: Bicarbonate Buffer |
| Adult: ETVAX (Full) + 10 ug dmLT | Experimental | 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 Receives: Biological: ETVAX; Biological: dmLT; Other: Bicarbonate Buffer |
| Adult: Placebo | Placebo comparator | Adult arm (18-45 year olds) receiving a placebo on days 0 and 14 Receives: Other: Bicarbonate Buffer |
| 24-59 months: ETVAX (1/4) | Experimental | 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 Receives: Biological: ETVAX; Other: Bicarbonate Buffer |
| 24-59 months: ETVAX (1/2) | Experimental | 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 Receives: Biological: ETVAX; Other: Bicarbonate Buffer |
| 24-59 months: ETVAX (full) | Experimental | 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 Receives: Biological: ETVAX; Other: Bicarbonate Buffer |
| 24-59 months: ETVAX (1/2) + 2.5 ug dmLT | Experimental | 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 Receives: Biological: ETVAX; Biological: dmLT; Other: Bicarbonate Buffer |
| 24-59 months: ETVAX (1/2) + 5 ug dmLT | Experimental | 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 Receives: Biological: ETVAX; Biological: dmLT; Other: Bicarbonate Buffer |
| 24-59 months: ETVAX (1/2) + 10 ug dmLT | Experimental | 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 Receives: Biological: ETVAX; Biological: dmLT; Other: Bicarbonate Buffer |
| 24-59 months: Placebo | Placebo comparator | 24-59 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14 Receives: Other: Bicarbonate Buffer |
| 12-23 months: ETVAX (1/4) | Experimental | 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 Receives: Biological: ETVAX; Other: Bicarbonate Buffer |
| 12-23 months: ETVAX (1/2) | Experimental | 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 Receives: Biological: ETVAX; Other: Bicarbonate Buffer |
| 12-23 months: ETVAX (1/2) + 2.5 ug dmLT | Experimental | 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 Receives: Biological: ETVAX; Biological: dmLT; Other: Bicarbonate Buffer |
| 12-23 months: ETVAX (1/2) + 5 ug dmLT | Experimental | 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 Receives: Biological: ETVAX; Biological: dmLT; Other: Bicarbonate Buffer |
| 12-23 months: Placebo | Placebo comparator | 12-23 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14 Receives: Other: Bicarbonate Buffer |
| 6-11 months: ETVAX (1/8) | Experimental | 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 Receives: Biological: ETVAX; Other: Bicarbonate Buffer |
| 6-11 months: ETVAX (1/4) | Experimental | 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 Receives: Biological: ETVAX; Other: Bicarbonate Buffer |
| 6-11 months: ETVAX (1/2) | Experimental | 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 Receives: Biological: ETVAX; Other: Bicarbonate Buffer |
| 6-11 months: ETVAX (1/4) + 2.5 ug dmLT | Experimental | 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 Receives: Biological: ETVAX; Biological: dmLT; Other: Bicarbonate Buffer |
| 6-11 month olds: ETVAX (1/4) + 5 ug dmLT | Experimental | 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 Receives: Biological: ETVAX; Biological: dmLT; Other: Bicarbonate Buffer |
| 6-11 month olds: Placebo | Placebo comparator | 6-11 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14 Receives: Other: Bicarbonate Buffer |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Between baseline and post-immunization (measured 7 days after the first dose and 5 days after the second). Antigen in ETVAX were:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 19 days
Number of Antigen Responses in Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Experienced by Subjects
Measured: 19 days
Number of Antigen Responses in Plasma Immunoglobulin A (IgA) Experienced by Subjects
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 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:
- 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
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2015 (estimated)
- Study startOct 2015
- Primary completion29 Jul 2017
- Study completion29 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Escherichia Coli DiarrheaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 475 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Collaborators
- Scandinavian Biopharma AB, International Centre for Diarrhoeal Disease Research, Bangladesh
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02531802
- Sponsor's protocol ID
- VAC 014
- Acronym
- ETVAX/dmLT
- Status last verified
- Sep 2018
- First submitted
- 17 Aug 2015
- Last updated
- 12 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 35536001Qadri 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.
PubMed 31757774Akhtar 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.
PubMed 30473185
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02531802
- Acronym / sponsor ID
- ETVAX/dmLT / VAC 014
- Conditions
- Escherichia Coli Diarrhea
- Keywords
- ETEC diarrhea, Escherichia Coli (ETEC)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 475 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Collaborators
- Scandinavian Biopharma AB, International Centre for Diarrhoeal Disease Research, Bangladesh
- Study start
- Oct 2015
- Primary completion
- 29 Jul 2017 (actual)
- Study completion
- 29 Jul 2017 (actual)
- First posted
- 24 Aug 2015 (estimated)
- Results
- Posted 12 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 21
| Arm | Type | Receives |
|---|---|---|
| Adult: ETVAX (Full) | Experimental | Biological: ETVAX, Other: Bicarbonate BufferAdult 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 | Experimental | Biological: ETVAX, Biological: dmLT, Other: Bicarbonate BufferAdult 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 comparator | Other: Bicarbonate BufferAdult arm (18-45 year olds) receiving a placebo on days 0 and 14 |
| 24-59 months: ETVAX (1/4) | Experimental | Biological: ETVAX, Other: Bicarbonate Buffer24-59 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) | Experimental | Biological: ETVAX, Other: Bicarbonate Buffer24-59 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) | Experimental | Biological: ETVAX, Other: Bicarbonate Buffer24-59 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 | Experimental | Biological: ETVAX, Biological: dmLT, Other: Bicarbonate Buffer24-59 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 | Experimental | Biological: ETVAX, Biological: dmLT, Other: Bicarbonate Buffer24-59 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 | Experimental | Biological: ETVAX, Biological: dmLT, Other: Bicarbonate Buffer24-59 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 comparator | Other: Bicarbonate Buffer24-59 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14 |
| 12-23 months: ETVAX (1/4) | Experimental | Biological: ETVAX, Other: Bicarbonate Buffer12-23 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) | Experimental | Biological: ETVAX, Other: Bicarbonate Buffer12-23 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 | Experimental | Biological: ETVAX, Biological: dmLT, Other: Bicarbonate Buffer12-23 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 | Experimental | Biological: ETVAX, Biological: dmLT, Other: Bicarbonate Buffer12-23 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 comparator | Other: Bicarbonate Buffer12-23 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14 |
| 6-11 months: ETVAX (1/8) | Experimental | Biological: ETVAX, Other: Bicarbonate Buffer6-11 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) | Experimental | Biological: ETVAX, Other: Bicarbonate Buffer6-11 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) | Experimental | Biological: ETVAX, Other: Bicarbonate Buffer6-11 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 | Experimental | Biological: ETVAX, Biological: dmLT, Other: Bicarbonate Buffer6-11 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 | Experimental | Biological: ETVAX, Biological: dmLT, Other: Bicarbonate Buffer6-11 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 comparator | Other: Bicarbonate Buffer6-11 month old children receiving a placebo of bicarbonate buffer solution administered orally on Day 0 and 14 |
Who may qualify
- Ages
- 6 months to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (44 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ETVAXVarying 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. | Biological | 12-23 months: ETVAX (1/2), 12-23 months: ETVAX (1/2) + 2.5 ug dmLT, 12-23 months: ETVAX (1/2) + 5 ug dmLT, 12-23 months: ETVAX (1/4), 24-59 months: ETVAX (1/2), 24-59 months: ETVAX (1/2) + 10 ug dmLT, 24-59 months: ETVAX (1/2) + 2.5 ug dmLT, 24-59 months: ETVAX (1/2) + 5 ug dmLT, 24-59 months: ETVAX (1/4), 24-59 months: ETVAX (full), 6-11 month olds: ETVAX (1/4) + 5 ug dmLT, 6-11 months: ETVAX (1/2), 6-11 months: ETVAX (1/4), 6-11 months: ETVAX (1/4) + 2.5 ug dmLT, 6-11 months: ETVAX (1/8), Adult: ETVAX (Full), Adult: ETVAX (Full) + 10 ug dmLT |
| dmLTAlso: double mutant heat labile toxin, LT(R192G/L211A)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. | Biological | 12-23 months: ETVAX (1/2) + 2.5 ug dmLT, 12-23 months: ETVAX (1/2) + 5 ug dmLT, 24-59 months: ETVAX (1/2) + 10 ug dmLT, 24-59 months: ETVAX (1/2) + 2.5 ug dmLT, 24-59 months: ETVAX (1/2) + 5 ug dmLT, 6-11 month olds: ETVAX (1/4) + 5 ug dmLT, 6-11 months: ETVAX (1/4) + 2.5 ug dmLT, Adult: ETVAX (Full) + 10 ug dmLT |
| Bicarbonate BufferSodium bicarbonate buffer dissolved in 150 ml of potable water | Other | 12-23 months: ETVAX (1/2), 12-23 months: ETVAX (1/2) + 2.5 ug dmLT, 12-23 months: ETVAX (1/2) + 5 ug dmLT, 12-23 months: ETVAX (1/4), 12-23 months: Placebo, 24-59 months: ETVAX (1/2), 24-59 months: ETVAX (1/2) + 10 ug dmLT, 24-59 months: ETVAX (1/2) + 2.5 ug dmLT, 24-59 months: ETVAX (1/2) + 5 ug dmLT, 24-59 months: ETVAX (1/4), 24-59 months: ETVAX (full), 24-59 months: Placebo, 6-11 month olds: ETVAX (1/4) + 5 ug dmLT, 6-11 month olds: Placebo, 6-11 months: ETVAX (1/2), 6-11 months: ETVAX (1/4), 6-11 months: ETVAX (1/4) + 2.5 ug dmLT, 6-11 months: ETVAX (1/8), Adult: ETVAX (Full), Adult: ETVAX (Full) + 10 ug dmLT, Adult: Placebo |
Primary outcome
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)
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.
Number and Percentage of Participants Experiencing Unsolicited Adverse Events Related to Vaccine
Time frame: 6 months ± 14 days after the first dose
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.
32 secondary outcomes
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
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
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 Fold Change of 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 ≥Two-fold Increase in Fecal Secretory Immunoglobulin A (SIgA) Response, by Antigen
Time frame: 28 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
Geometric Mean Titer (GMT) of Fecal Secretory Immunoglobulin A (SIgA) Response 6-11 Month Old Subjects, by Antigen
Time frame: 28 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 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
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
Geometric Mean Titer (GMT) of 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 Antigens in ETVAX
Time frame: 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
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
Geometric Mean Fold Change in Plasma Immunoglobulin A (IgA) Response After Either Vaccine Dose, for O78 Antigen, Among Adults
Time frame: 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
Time frame: 19 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
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
Number of Antigen Responses in Antibody Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Experienced by Subjects
Time frame: 19 days
Number of Antigen Responses in Plasma Immunoglobulin A (IgA) Experienced by Subjects
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 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 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 Fold Change of Fecal Secretory Immunoglobulin A (SIgA) Response Among 6-11 Month Old Subjects on Day 7, by Antigen
Time frame: 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
Time frame: 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
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 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 28, by Antigen
Time frame: 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
Time frame: 28 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 28, by Antigen
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35536001Higginson 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.
- Derived from this study: PubMed 31757774Qadri 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.
- Derived from this study: PubMed 30473185Akhtar 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ETVAX, dmLT and Bicarbonate Buffer in people with Escherichia Coli Diarrhea, run by PATH at 1 site in Bangladesh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bangladesh. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02531802, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2018; AzTrials last refreshed its copy on 8 Nov 2026.