Clinical trial NCT03220737: VAXCHORA Pediatric Study to Assess Safety and Immunogenicity
Official title: A Phase 4 Study to Assess the Safety and Immunogenicity of VAXCHORA (Cholera Vaccine, Live, Oral) in Children 2 to <18 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cholera (Disorder)
Lead sponsor: Bavarian Nordic
Sponsor class: INDUSTRY
Collaborators: name: Emergent BioSolutions
First posted: 2017-07-18
Enrollment: 550
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Cohort 1 (12-17 Yrs) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae
timeFrame: Day 11
measure: Cohort 2 (6 to <12 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae
timeFrame: Day 11
measure: Cohort 3 (2 to <6 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae
timeFrame: Day 11
measure: Cohort 1 (12-17 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years
timeFrame: Day 11
measure: Cohort 2 (6-11 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years
timeFrame: Day 11
measure: Cohort 3 (2-5 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years
timeFrame: Day 11
Secondary outcomes:
measure: Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 29
timeFrame: Day 29
measure: Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 91
timeFrame: Day 91
measure: Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 181
timeFrame: Day 181
measure: Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 365
timeFrame: Day 365
measure: Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 547
timeFrame: Day 547
measure: Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 730
timeFrame: Day 730
measure: Cohort 2 (6 to <12 Years) - Seroconversion of SVA - Day 29
timeFrame: Day 29
measure: Cohort 3 (2 to <6 Years) - Seroconversion of SVA - Day 29
timeFrame: Day 29
Other outcomes:
measure: Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 1
timeFrame: Day 1
measure: Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 91
timeFrame: Day 91
measure: Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 181
timeFrame: Day 181
measure: Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 365
timeFrame: Day 365
measure: Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 547
timeFrame: Day 547
measure: Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 730
timeFrame: Day 730
measure: Safety - Solicited Adverse Events
timeFrame: Through Day 8
measure: Safety - Unsolicited Adverse Events
timeFrame: Through Day 29
measure: Safety - Serious Adverse Events
timeFrame: Through Day 181
measure: Acceptability
timeFrame: Day 1
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Lenexa
country: United States
facility: Johnson County Clin-Trials, Inc.
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Kansas City
country: United States
facility: The Center for Pharmaceutical Research
state: Missouri
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc.
state: New York
city: Columbus
country: United States
facility: Aventiv Research Inc.
state: Ohio
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Nashville
country: United States
facility: Clinical Research Associates, Inc.
state: Tennessee
Study officials:
affiliation: Emergent BioSolutions
name: Paul Andre de Lame, MD
role: STUDY_DIRECTOR
References:
citation: McCarty JM, Gierman EC, Bedell L, Lock MD, Bennett S. Safety and Immunogenicity of Live Oral Cholera Vaccine CVD 103-HgR in Children and Adolescents Aged 6-17 Years. Am J Trop Med Hyg. 2020 Jan;102(1):48-57. doi: 10.4269/ajtmh.19-0241.