Clostridium Difficile Vaccine 2-Dose Versus 3-Dose Study

Study Overview
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Brief Summary
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This study will investigate a Clostridium difficile vaccine in healthy adults 50 years of age and older. In half the healthy adults, all 3 doses given are the Clostridium difficile vaccine, and in half the healthy adults, 2 of the 3 doses are the Clostridium difficile vaccine with the other dose containing no active ingredients. The study will look at the subjects' immune response to the vaccine and assess the safety and tolerability of a 2-dose regimen of Clostridium difficile vaccine compared to a 3-dose regimen of Clostridium difficile vaccine.

Official Title
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A PHASE 3, RANDOMIZED OBSERVER-BLINDED STUDY TO EVALUATE THE IMMUNOGENICITY, SAFETY, AND TOLERABILITY OF 2 DOSES COMPARED TO 3 DOSES OF CLOSTRIDIUM DIFFICILE VACCINE IN ADULTS 50 YEARS OF AGE AND OLDER

Conditions
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Clostridium Difficile Associated Disease

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence of a personally signed and dated informed consent document. Willing and able to comply with study procedures. Subjects with an increased risk of future contact with healthcare systems or subjects who have received systemic antibiotics in the previous 12 weeks. Ability to be contacted by telephone during study participation. Exclusion Criteria: Pregnant female participants; breastfeeding female participants; positive urine pregnancy test for women of childbearing potential (WOCBP); and WOCBP who are, in the opinion of the investigator, sexually active and at risk for pregnancy and are unwilling or unable to use effective methods of contraception as outlined in this protocol from the signing of the informed consent until at least 28 days after the last dose of investigational product. Prior episode of CDI, confirmed by either laboratory test or diagnosis of pseudomembranous colitis at colonoscopy, at surgery, or histopathologically. Participants who may be unable to respond to vaccination due to: Metastatic malignancy; or End-stage renal disease (glomerular filtration rate <15 mL/min/1.73 m2 or on dialysis). Any serious medical disorder that in the investigator's opinion is likely to be fatal within the next 12 months. Congenital or acquired immunodeficiency. Known infection with human immunodeficiency virus (HIV). Any bleeding disorder or anticoagulant therapy that would contraindicate IM injection. Any contraindication to vaccination or vaccine components, including previous anaphylactic reaction to any vaccine or vaccine-related components. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. Previous administration of an investigational C difficile vaccine or C difficile mAb therapy. Receipt of systemic corticosteroids for greater than or equal to 14 days within 28 days before enrollment. Receipt of chronic systemic treatment with other known immunosuppressant medications, or radiotherapy, within 6 months before enrollment. Receipt of blood products or immunoglobulins within 6 months before enrollment. Participation in other studies involving investigational drug(s)/vaccine(s) within 28 days prior to study entry until 1 month after the third vaccination. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.

Ages Eligible for Study
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Minimum Age: 50 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clostridium difficile vaccine - 3 dose<br>All 3 doses are the Clostridium difficile vaccine | Biological: Clostridium difficile<br>* Toxoid-based Clostridium difficile vaccine<br>|
| Experimental: Clostridium difficile vaccine - 2 dose<br>2 of the 3 doses are the Clostridium difficile vaccine with the other being placebo | Biological: Clostridium difficile<br>* Toxoid-based Clostridium difficile vaccine<br>Biological: Placebo<br>* Normal saline solution (0.9% sodium chloride)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C difficile toxin A- and toxin B-specific neutralizing antibody levels at Month 7 in each regimen | As measured by the central laboratory | At Month 7 | 
| Percentage of subjects reporting local reactions | Pain, erythema, and induration, as self-reported in electronic diaries | Up to 7 days following each vaccination | 
| Percentage of subjects reporting systemic events | Fever, vomiting, headache, fatigue, new or worsening muscle pain, and new or worsening joint pain, as self-reported in electronic diaries | Up to 7 days following each vaccination | 
| Percentage of subjects reporting nonserious adverse events | As elicited by investigational site staff | Up to 1 month after the last dose of vaccine | 
| Percentage of subjects reporting serious adverse evets | As elicited by investigational site staff | Up to 6 months after the last dose of vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxin A- and toxin B-specific neutralizing antibody levels, expressed as geometric mean concentrations in each regimen | As measured by the central laboratory | At Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clostridium Difficile, vaccine