VAXCHORA Pediatric Study to Assess Safety and Immunogenicity

Study Overview
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Brief Summary
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VAXCHORA (Cholera Vaccine, Live, Oral) is a vaccine indicated for active immunization against disease caused by Vibrio cholerae serogroup O1. VAXCHORA is approved for use in adults 18 through 64 years of age travelling to cholera-affected areas. The primary goals of this Phase 4 study are to evaluate the safety and immunogenicity of a single dose of VAXCHORA (1 x 10e9 cfu/dose) in children ages 2 years to <18 years of age in developed countries.

Detailed Description
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This is a randomized, placebo-controlled, double-blind, single-crossover study with three age cohorts and two treatment groups within each cohort.

Official Title
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A Phase 4 Study to Assess the Safety and Immunogenicity of VAXCHORA (Cholera Vaccine, Live, Oral) in Children 2 to <18 Years of Age

Conditions
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Cholera (Disorder)

Intervention / Treatment
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* Biological: VAXCHORA (Cholera Vaccine, Live, Oral)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female Between 2 and <18 years of age on Day 1 In general good health Able and willing to provide informed assent for study participation Primary caregiver is able and willing to provide informed consent for study participation (for females of childbearing potential) Using an acceptable method of contraception through Day 29 Exclusion Criteria: Current acute gastrointestinal illness or loose stools within 3 days of Day 1 visit Current acute febrile illness History of cholera infection History of cholera vaccination History of severe allergic reaction (e.g. anaphylaxis) to any ingredient of VAXCHORA Congenital or acquired immunodeficiency Pregnancy (for females of childbearing potential) Any other condition that, in the opinion of the Investigator, creates an unacceptable risk to the subject Any other condition that, in the opinion of the Investigator, will interfere with the conduct of the study or the validity of the data Duration of >2 weeks of abnormal stool pattern, defined as <3 stools per week or >2 stools per day in the past 6 months Regular use of laxatives in the past 6 months History of enterotoxigenic E. coli infection Travel to cholera-endemic area in the previous 5 years Nursing/Breastfeeding 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 Received or plans to receive any other investigational agent throughout the main study (Day 181)

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is a randomized, placebo-controlled, double-blind, single-crossover study with three age cohorts and two treatment groups within each cohort. The main study consists of a screening period of 30 days, a treatment period from Day 1 to Day 29, and a follow-up period through Day 181. Cohort 1 has an optional sub-study consisting of a long-term follow-up period through Day 730.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (active, 12-17 yrs)<br>Subjects aged 12 - 17 were administered a 100 mL oral dose of Vaxchora vaccine on Day 1, and had study visits on Day 11, 29, 91 and 181. Cohort 1 subjects that continued in the long-term follow-up sub-study had visits on days 365, 547 and 730. | Biological: VAXCHORA (Cholera Vaccine, Live, Oral)<br>* VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR.<br>|
| Placebo Comparator: Cohort 1 (placebo, 12 - 17 yrs)<br>Subjects aged 12 - 17 were administered a 100 mL oral dose of 0.9% saline on Day 1, and had study visits on Day 11, 29, 91 and 181. | Other: Placebo<br>* Placebo control for this study is normal (0.9%) saline.<br>|
| Experimental: Cohort 2 (active, 6 - 11 yrs)<br>Subjects aged 6 - 11 were administered a 100 mL oral dose of Vaxchora vaccine on Day 1, and had study visits on Day 11, 29, 91 and 181. | Biological: VAXCHORA (Cholera Vaccine, Live, Oral)<br>* VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR.<br>|
| Placebo Comparator: Cohort 2 (placebo, 6 - 11 yrs)<br>Subjects aged 6 - 11 were administered a 100 mL oral dose of 0.9% saline on Day 1, and had study visits on Day 11, 29, 91 and 181. | Other: Placebo<br>* Placebo control for this study is normal (0.9%) saline.<br>|
| Experimental: Cohort 3 (active, 2 - 5 yrs)<br>Subjects aged 2 - 5 were administered a 50 mL oral dose of Vaxchora vaccine on Day 1, and had study visits on Day 11, 29, 91 and 181. | Biological: VAXCHORA (Cholera Vaccine, Live, Oral)<br>* VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR.<br>|
| Placebo Comparator: Cohort 3 (placebo, 2 - 5 yrs)<br>Subjects aged 2-5 were administered a 50 mL oral dose of 0.9% saline on Day 1, and had study visits on Day 11, 29, 91 and 181. | Other: Placebo<br>* Placebo control for this study is normal (0.9%) saline.<br>|
| Other: Historical Control: Adult Bridging Population<br>This arm consists of historical data from Vaxchora vaccine subjects from study PXVX-VC-200-004. The data was included in study PXVX-VC-200-006 as a comparator bridging population for the Day 11 seroconversion. NCT02094586 PubMed ID:29317118 | Biological: VAXCHORA (Cholera Vaccine, Live, Oral)<br>* VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1 (12-17 Yrs) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae | 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 | Day 11 | 
| Cohort 2 (6 to <12 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae | 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. | Day 11 | 
| Cohort 3 (2 to <6 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae | 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. | Day 11 | 
| Cohort 1 (12-17 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years | The seroconversion rate is defined as the percentage of subjects with a 4-fold or greater rise over baseline Day 1 Serum Vibriocidal Antibody (SVA) titer against the classical Inaba biotype of V. cholerae at Day 11 following one dose of Vaxchora vaccine. The hypothesis was that the pediatric seroconversion rate would be non-inferior to the seroconversion rate at Day 11 in adults between the ages of 18 and 45 years. | Day 11 | 
| Cohort 2 (6-11 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years | The seroconversion rate is defined as the percentage of subjects with a 4-fold or greater rise over baseline Day 1 Serum Vibriocidal Antibody (SVA) titer against the classical Inaba biotype of V. cholerae at Day 11 following one dose of Vaxchora vaccine. The hypothesis was that the pediatric seroconversion rate would be non-inferior to the seroconversion rate at Day 11 in adults between the ages of 18 and 45 years. | Day 11 | 
| Cohort 3 (2-5 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years | The seroconversion rate is defined as the percentage of subjects with a 4-fold or greater rise over baseline Day 1 Serum Vibriocidal Antibody (SVA) titer against the classical Inaba biotype of V. cholerae at Day 11 following one dose of Vaxchora vaccine. The hypothesis was that the pediatric seroconversion rate would be non-inferior to the seroconversion rate at Day 11 in adults between the ages of18 and 45 years. | Day 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 29 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 29 for all subjects | Day 29 | 
| Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 91 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 91 for all subjects | Day 91 | 
| Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 181 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 181 for all subjects | Day 181 | 
| Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 365 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 365 for all subjects | Day 365 | 
| Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 547 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 547 for all subjects | Day 547 | 
| Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 730 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 730 for all subjects | Day 730 | 
| Cohort 2 (6 to <12 Years) - Seroconversion of SVA - Day 29 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 29 for all subjects | Day 29 | 
| Cohort 3 (2 to <6 Years) - Seroconversion of SVA - Day 29 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 29 for all subjects | Day 29 |