VAXCHORA Pediatric Study to Assess Safety and Immunogenicity

NCT03220737 | Completed Phase 4 Results FDA Drug

• 1 other identifier: PXVX-VC-200-006
• Study Type: interventional
• Target: 550
• Locations: 1 country
• Sites: 10

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.

Conditions

Cholera (Disorder)

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (8)

• Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 29

  Day 29

• Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 91

  Day 91

• Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 181

  Day 181

• Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 365

  Day 365

• Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 547

  Day 547

Other Outcomes (10)

• Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 1

  Day 1

• Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 91

  Day 91

• Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 181

  Day 181

Study Arms (7)

Cohort 1 (active, 12-17 yrs)

EXPERIMENTAL

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)

Cohort 1 (placebo, 12 - 17 yrs)

PLACEBO COMPARATOR

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

Cohort 2 (active, 6 - 11 yrs)

EXPERIMENTAL

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)

Cohort 2 (placebo, 6 - 11 yrs)

PLACEBO COMPARATOR

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

Cohort 3 (active, 2 - 5 yrs)

EXPERIMENTAL

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)

Cohort 3 (placebo, 2 - 5 yrs)

PLACEBO COMPARATOR

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

Historical Control: Adult Bridging Population

OTHER

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)

Interventions

VAXCHORA (Cholera Vaccine, Live, Oral) BIOLOGICAL

VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR.

Cohort 1 (active, 12-17 yrs); Cohort 2 (active, 6 - 11 yrs); Cohort 3 (active, 2 - 5 yrs); Historical Control: Adult Bridging Population

Placebo OTHER

Placebo control for this study is normal (0.9%) saline.

Cohort 1 (placebo, 12 - 17 yrs); Cohort 2 (placebo, 6 - 11 yrs); Cohort 3 (placebo, 2 - 5 yrs)

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bavarian Nordic: lead
• Emergent BioSolutions: collaborator

Study Sites (10)

Emory University

Atlanta, Georgia, 30322, United States

Location

Johnson County Clin-Trials, Inc.

Lenexa, Kansas, 66219, United States

Location

Heartland Research Associates, LLC

Wichita, Kansas, 67207, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

The Center for Pharmaceutical Research

Kansas City, Missouri, 64114, United States

Location

Rochester Clinical Research, Inc.

Rochester, New York, 14609, United States

Location

Aventiv Research Inc.

Columbus, Ohio, 43123, United States

Location

Coastal Carolina Research Center

Mt. Pleasant, South Carolina, 29464, United States

Location

Clinical Research Associates, Inc.

Nashville, Tennessee, 37203, United States

Location

Related Publications (1)

• 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.

  PMID: 31769402 DERIVED

MeSH Terms

Conditions

Cholera

Interventions

Vaxchora; Cholera Vaccines

Condition Hierarchy (Ancestors)

Vibrio Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: David Cassie, Scientist, Clinical Research
• Organization: Emergent BioSolutions Canada Inc.

dcassie@ebsi.com

204-275-4589

Study Officials

• Paul Andre de Lame, MD

  Emergent BioSolutions

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study will be conducted as a double-blind study through 181, where neither the sponsor, the statistical team, study volunteer subjects, nor clinical site personnel (except for the unblinded administration staff) will know subjects' treatment assignment. Once each subject has reached their Day 181 visit they will be individually unblinded.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: July 18, 2017
• Study Start: July 21, 2017
• Primary Completion: September 10, 2019
• Study Completion: March 6, 2020
• Last Updated: June 28, 2023
• Results First Posted: November 19, 2020

Record last verified: 2023-06

Locations

US (10)