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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Clostridium Difficile Associated Disease

Intervention / Treatment
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* Biological: Clostridium difficile Vaccine
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female adults Aged 65 to 85 years Exclusion Criteria: Proven or suspected prior episode of Clostridium difficile associated diarrhea Unstable chronic medical condition Disease requiring significant change in therapy or hospitalization for worsening disease within 8 weeks before receipt of study vaccine Serious chronic medical disorders Bleeding diathesis or condition associated with prolonged bleeding time that may contraindicate intramuscular injection Any contraindication to vaccination or vaccine components, including previous anaphylactic reaction to any vaccine or vaccine-related components Subjects with congenital or acquired immunodeficiency disorders Subjects with rheumatologic disorders or other illnesses requiring chronic treatment with known immunosuppressant medications Active or treated leukemia or lymphoma or bone marrow disorder Residence in a nursing home or other long-term care facility, or requirement for semiskilled nursing care or assisted living Abnormality in screening hematology and/or blood chemistry laboratory values

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |