VAXCHORA Pediatric Study to Assess Safety and Immunogenicity

Phase 4

Completed

Conditions: Cholera (Disorder)

Interventions: Biological: VAXCHORA (Cholera Vaccine, Live, Oral)
Other: Placebo

Registration Number: NCT03220737

Lead Sponsor: Bavarian Nordic

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 550

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1 (active, 12-17 yrs)	VAXCHORA (Cholera Vaccine, Live, Oral)	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.
Cohort 3 (placebo, 2 - 5 yrs)	Placebo	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.
Historical Control: Adult Bridging Population	VAXCHORA (Cholera Vaccine, Live, Oral)	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
Cohort 3 (active, 2 - 5 yrs)	VAXCHORA (Cholera Vaccine, Live, Oral)	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.
Cohort 1 (placebo, 12 - 17 yrs)	Placebo	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.
Cohort 2 (active, 6 - 11 yrs)	VAXCHORA (Cholera Vaccine, Live, Oral)	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.
Cohort 2 (placebo, 6 - 11 yrs)	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Cohort 2 (6 to <12 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae	Day 11	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.
Cohort 3 (2 to <6 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae	Day 11	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.
Cohort 2 (6-11 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years	Day 11	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.
Cohort 1 (12-17 Yrs) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae	Day 11	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
Cohort 1 (12-17 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years	Day 11	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.
Cohort 3 (2-5 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years	Day 11	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.

Secondary Outcome Measures

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

Trial Locations

Locations (10): Emory University
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Atlanta, Georgia, United States
Aventiv Research Inc.
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Columbus, Ohio, United States
Johnson County Clin-Trials, Inc.
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Lenexa, Kansas, United States
Heartland Research Associates, LLC
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Wichita, Kansas, United States
Rochester Clinical Research, Inc.
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Rochester, New York, United States
Coastal Carolina Research Center
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Mount Pleasant, South Carolina, United States
Boston Medical Center
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Boston, Massachusetts, United States
The Center for Pharmaceutical Research
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Kansas City, Missouri, United States
Clinical Research Associates, Inc.
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Nashville, Tennessee, United States
University of Kentucky
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Lexington, Kentucky, United States