Clostridium Difficile Vaccine Safety, Tolerability, and Immunogenicity Study in Japanese Adults

A Phase 1, Placebo-controlled, Randomized, Observer-blinded Study To Evaluate The Safety, Tolerability, And Immunogenicity Of Two 3-dose Regimens Of Clostridium Difficile Vaccine Administered In Healthy Japanese Adults Aged 65 To 85 Years.

The first-in-Japanese study B5091010 has been designed to evaluate the safety, tolerability, and immunogenicity of 2 antigen dose levels of C difficile vaccine when administered as one of two 3-dose regimens to healthy Japanese adults aged 65 to 85 years.

Study Overview

• Status: Completed
• Conditions: Clostridium Difficile Associated Disease
• Intervention / Treatment: Biological: Clostridium difficile Vaccine; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-0025
    • SOUSEIKAI PS Clinic (formerly Medical Co. LTA PS Clinic)
  • Tokyo
    • Sumida-ku, Tokyo, Japan, 130-0004
      • SOUSEIKAI Sumida Hospital (formerly Medical Co. LTA Sumida Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 85 years (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male and female adults
2. Aged 65 to 85 years

Exclusion Criteria:

1. Proven or suspected prior episode of Clostridium difficile associated diarrhea
2. Unstable chronic medical condition
3. Disease requiring significant change in therapy or hospitalization for worsening disease within 8 weeks before receipt of study vaccine
4. Serious chronic medical disorders
5. Bleeding diathesis or condition associated with prolonged bleeding time that may contraindicate intramuscular injection
6. Any contraindication to vaccination or vaccine components, including previous anaphylactic reaction to any vaccine or vaccine-related components
7. Subjects with congenital or acquired immunodeficiency disorders
8. Subjects with rheumatologic disorders or other illnesses requiring chronic treatment with known immunosuppressant medications
9. Active or treated leukemia or lymphoma or bone marrow disorder
10. Residence in a nursing home or other long-term care facility, or requirement for semiskilled nursing care or assisted living
11. Abnormality in screening hematology and/or blood chemistry laboratory values

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dose C. difficile Vaccine (accelerated schedule)	Biological: Clostridium difficile Vaccine; 0.5 mL intramuscular injection
Experimental: High-dose C. difficile Vaccine (accelerated schedule)	Biological: Clostridium difficile Vaccine; 0.5 mL intramuscular injection
Placebo Comparator: Placebo (accelerated schedule)	Biological: Placebo; 0.5 mL intramuscular injection
Experimental: Low-dose C. difficile Vaccine (non-accelerated schedule)	Biological: Clostridium difficile Vaccine; 0.5 mL intramuscular injection
Experimental: High-dose C. difficile Vaccine (non-accelerated schedule)	Biological: Clostridium difficile Vaccine; 0.5 mL intramuscular injection
Placebo Comparator: Placebo (non-accelerated schedule)	Biological: Placebo; 0.5 mL intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportions of subjects reporting local reactions (pain, erythema, and induration) and their severity, as self-reported on e-diaries	Up to 14 days after each vaccination
Proportions of subjects reporting systemic events (fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, and new or worsening joint pain) and their severity, as self-reported on e-diaries	Up to 14 days after each vaccination
Proportions of subjects reporting AEs (categorized according to the Medical Dictionary for Regulatory Activities [MedDRA])	From the first vaccination up to 28 days after the last vaccination
Proportions of subjects reporting SAEs (categorized according to the Medical Dictionary for Regulatory Activities [MedDRA])	From the first vaccination until 6 months after the last vaccination
Proportions of subjects with abnormal hematology and blood chemistry laboratory assessments	7 days or 14 days after each vaccination

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxin A- and toxin B-specific neutralizing antibody levels, expressed as geometric mean concentrations	Up to 6 months after dose 3
Geometric mean fold rises in toxin A- and toxin B-specific neutralizing antibody levels	Up to 6 months after dose 3
Proportions of subjects in each vaccine group with toxin A-specific neutralizing antibody level ≥ the specified threshold for toxin A	Up to 6 months after dose 3
Proportions of subjects in each vaccine group with toxin B-specific neutralizing antibody level ≥ the specified threshold for toxin B	Up to 6 months after dose 3
Proportions of subjects in each vaccine group with both toxin A- and toxin B-specific neutralizing antibody levels ≥ the specified threshold for toxin A and the specified threshold for toxin B, respectively	Up to 6 months after dose 3
Proportions of subjects in each vaccine group with fold rises in toxin A-specific neutralizing antibody levels	Up to 6 months after dose 3
Proportions of subjects in each vaccine group with fold rises in toxin B-specific neutralizing antibody levels	Up to 6 months after dose 3
Proportions of subjects in each vaccine group with fold rises in both toxin A- and toxin B-specific neutralizing antibody levels	Up to 6 months after dose 3

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Inoue M, Yonemura T, de Solom R, Yamaji M, Aizawa M, Knirsch C, Pride MW, Jansen KU, Gruber W, Webber C. A phase 1 randomized study assessing safety and immunogenicity of two 3-dose regimens of a Clostridium difficile vaccine in healthy older Japanese adults. Vaccine. 2019 May 1;37(19):2600-2607. doi: 10.1016/j.vaccine.2019.03.014. Epub 2019 Apr 5.

Helpful Links

• To obtain contact information for a study center near you, click here.
• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: January 29, 2016
• First Submitted That Met QC Criteria: March 28, 2016
• First Posted (Estimate): April 1, 2016

Study Record Updates

• Last Update Posted (Actual): July 13, 2018
• Last Update Submitted That Met QC Criteria: July 11, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Clostridium Infections
• Other Study ID Numbers: B5091010