E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of severe diarrhoea caused by cholera bacteria |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047398 |
E.1.2 | Term | Vibrio cholerae gastroenteritis |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008632 |
E.1.2 | Term | Cholera due to Vibrio cholerae |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008634 |
E.1.2 | Term | Cholera, unspecified |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008633 |
E.1.2 | Term | Cholera due to Vibrio cholerae el tor |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045658 |
E.1.2 | Term | Unspecified cholera |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047397 |
E.1.2 | Term | Vibrio cholera gastroenteritis |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070172 |
E.1.2 | Term | Vibrio cholerae test positive |
E.1.2 | System Organ Class | 100000004848 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1) For each of Cohort 1: 12 to <18 years, Cohort 2: 6 to <12 years and Cohort 3: 2 to <6 years Primary Immunogenicity Objectives: • Demonstrate that the seroconversion rate at Day 11 in pediatric subjects is non-inferior to the seroconversion rate at Day 11 in adults between the ages of 18 and 45 years. • Demonstrate that the seroconversion rate in pediatric subjects is greater than or equal to 70% with 98.3% confidence. Primary Safety Objectives: Objective: • Evaluate the safety and clinical acceptability of VAXCHORA in children. • Evaluate the acceptability of VAXCHORA • Evaluate the palatability of VAXCHORA |
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E.2.2 | Secondary objectives of the trial |
1) For Cohort 1: 12 to <18 years Secondary Immunogenicity Objectives: • Seroconversion of serum vibriocidal antibody (SVA) against the classical Inaba biotype of V. cholerae at Days 29, 91 and 181 for all subjects. • Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Days 365, 547 and 730 for vaccinees participating in the sub-study. Exploratory Immunogenicity Objective: • Explore memory B cell response to VAXCHORA vaccination at each time point.
2) For each of Cohort 2: 6 to <12 years and Cohort 3: 2 to <6 years Secondary Immunogenicity Objective Evaluate seroconversion rate at Day 29
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The substudy does not have a separate protocol and is included in the main protocol. A subset of vaccinees in Cohort 1 will be evaluated for long term seroconversion and anti-O1 lipopolysaccharide memory B cell concentration at Days 365, 547 and 730. |
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E.3 | Principal inclusion criteria |
1. Male or female. 2. Between 2 and <18 years of age on Day 1. 3. In general good health. 4. Able and willing to provide informed assent for study participation. 5. Primary caregiver is able and willing to provide informed consent for study participation. 6. (for females of childbearing potential) Using an acceptable method of contraception through Day 29
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E.4 | Principal exclusion criteria |
1. Current acute gastrointestinal illness or loose stools within 3 days of Day 1 visit. 2. Current acute febrile illness. 3. History of cholera infection. 4. History of cholera vaccination. 5. History of severe allergic reaction (e.g. anaphylaxis) to any ingredient of VAXCHORA. 6. Congenital or acquired immunodeficiency. 7. (for females of childbearing potential) Pregnant 8. Any other condition that, in the opinion of the Investigator, creates an unacceptable risk to the subject. 9. Any other condition that, in the opinion of the Investigator, will interfere with the conduct of the study or the validity of the data. 10. Duration of >2 weeks of abnormal stool pattern, defined as <3 stools per week or >2 stools per day in the past 6 months. 11. Regular use of laxatives in the past 6 months. 12. History of enterotoxigenic E. coli infection. 13. Travel to cholera-endemic area in the previous 5 years. 14. Nursing/breastfeeding. 15. Received or plans to receive the following from 14 days prior to the study vaccination through 11 days after vaccination: Any other licensed vaccines Antibiotics or chloroquine or any other investigational agents. 16. Received or plans to receive any other investigational agent throughout the main study (Day 181).
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Immunogenicity endpoint • The proportion of subjects achieving seroconversion of serum vibriocidal antibody (SVA) against the classical Inaba biotype of V. cholerae at Day 11 following one dose of VAXCHORA, defined as a 4-fold or greater rise over baseline Day 1 SVA titer. This proportion of seroconverters is called the seroconversion rate. Primary Safety Endpoints • Solicited adverse events through Day 8: abdominal pain, headache, lack of appetite, tiredness, diarrhea, nausea, vomiting and fever, by age cohort and overall • Unsolicited adverse events through Day 29, by age cohort and overall • Serious adverse events through Day 181, by age cohort and overall. Acceptability Endpoint • The percent of subjects in each age cohort able to complete dosing according to protocol Palatability Endpoint • Palatability of vaccine assessed by the subject using a 5-point Hedonic scale in Cohorts 1 and 2. • Palatability of vaccine assessed by the caregiver using a 5-point Hedonic scale in Cohort 3 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Seroconversion rate will be measured at Day 11 Safety will be assessed by solicited adverse events through Day 8, unsolicicted adverse events through Day 29 and serious adverse events through Day 181 Acceptability and palatability will be assessed at Day 1 following dosing |
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E.5.2 | Secondary end point(s) |
1) For Cohort 1: 12 to <18 years Secondary immunogenicity endpoints • Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Days 29, 91 and 181 for all subjects. • Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Days 365, 547 and 730 for vaccinees participating in the sub-study Exploratory Immunogenicity Endpoint: • Associated memory B cell endpoints: Anti–O1 lipopolysaccharide (LPS) memory B cell concentration at Days 1, 91, 181 for the subjects in the active treatment group and the placebo crossover group and Days 365, 547, 730 for the subjects in the active treatment group who participate in the sub-study 2) For each of Cohort 2: 6 to <12 years and Cohort 3: 2 to <6 years Secondary immunogenicity endpoint Seroconversion of serum vibriocidal antibody (SVA) against the classical Inaba biotype of V. cholerae at Day 29 following one dose of VAXCHORA
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For Cohort 1: 12 to <18 years • Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Days 29, 91 and 181 for all subjects • and at Days 365, 547 and 730 for vaccinees participating in the sub-study Exploratory Immunogenicity Endpoint: • Associated memory B cell endpoints: Anti–O1 lipopolysaccharide (LPS) memory B cell concentration at Days 1, 91, 181 for the subjects in the active treatment group and the placebo crossover group and Days 365, 547, 730 for the subjects in the active treatment group who participate in the sub-study 2) For each of Cohort 2: 6 to <12 years and Cohort 3: 2 to <6 years Seroconversion of serum vibriocidal antibody (SVA) against the classical Inaba biotype of V. cholerae at Day 29 following one dose of VAXCHORA |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |