VAXCHORA Pediatric Study to Assess Safety and Immunogenicity

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

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.

Study Overview

• Status: Completed
• Conditions: Cholera (Disorder)
• Intervention / Treatment: Biological: VAXCHORA (Cholera Vaccine, Live, Oral); Other: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 550
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clin-Trials, Inc.
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • Ohio
    • Columbus, Ohio, United States, 43123
      • Aventiv Research Inc.
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 15 years (Child)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (active, 12-17 yrs); 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); VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR.
Placebo Comparator: Cohort 1 (placebo, 12 - 17 yrs); 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; Placebo control for this study is normal (0.9%) saline.
Experimental: Cohort 2 (active, 6 - 11 yrs); 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); VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR.
Placebo Comparator: Cohort 2 (placebo, 6 - 11 yrs); 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; Placebo control for this study is normal (0.9%) saline.
Experimental: Cohort 3 (active, 2 - 5 yrs); 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); VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR.
Placebo Comparator: Cohort 3 (placebo, 2 - 5 yrs); 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; Placebo control for this study is normal (0.9%) saline.
Other: Historical Control: Adult Bridging Population; 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); VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 1	Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 1 for the subjects in the active treatment group and the placebo crossover group	Day 1
Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 91	Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 91 for the subjects in the active treatment group and the placebo crossover group	Day 91
Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 181	Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 181 for the subjects in the active treatment group and the placebo crossover group	Day 181
Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 365	Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 365 for the subjects in the active treatment group who participate in the substudy.	Day 365
Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 547	Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 547 for the subjects in the active treatment group who participate in the substudy.	Day 547
Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 730	Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 730 for the subjects in the active treatment group who participate in the substudy.	Day 730
Safety - Solicited Adverse Events	Evaluate the safety and tolerability of VAXCHORA by collecting solicited adverse events (abdominal pain, headache, lack of appetite, tiredness, diarrhea, nausea, vomiting and fever) by age cohort and overall through Day 8	Through Day 8
Safety - Unsolicited Adverse Events	Evaluate the safety and tolerability of VAXCHORA by collecting unsolicited adverse events by age cohort and overall through Day 29	Through Day 29
Safety - Serious Adverse Events	Evaluate the safety and tolerability of VAXCHORA by collecting serious adverse events by age cohort and overall through Day 181	Through Day 181
Acceptability	Evaluate the acceptability of VAXCHORA using the percent of subjects in each age cohort able to complete the dosing according to protocol.	Day 1

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Collaborators: Emergent BioSolutions
• Investigators: Study Director: Paul Andre de Lame, MD, Emergent BioSolutions

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2017
• Primary Completion (Actual): September 10, 2019
• Study Completion (Actual): March 6, 2020

Study Registration Dates

• First Submitted: July 11, 2017
• First Submitted That Met QC Criteria: July 13, 2017
• First Posted (Actual): July 18, 2017

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vibrio Infections; Cholera
• Other Study ID Numbers: PXVX-VC-200-006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No