A Study To Investigate A Clostridium Difficile Vaccine In Healthy Adults Aged 50 to 85 Years, Who Will Each Receive 3 Doses Of Vaccine.

Study Overview
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Brief Summary
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This study will investigate a Clostridium difficile vaccine in healthy adults aged 50 to 85 years, who will each receive 3 doses of vaccine. The study will assess the safety and tolerability of the vaccine, and also look at the subjects' immune response to the vaccine.

Official Title
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A Phase 2, Placebo-controlled, Randomised, Observer-blinded Trial To Evaluate The Safety, Tolerability And Immunogenicity Of A Clostridium Difficile Vaccine Administered As A 3-dose Regimen In Healthy Adults Aged 50 To 85 Years

Conditions
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Clostridium Difficile Associated Disease

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects aged 50 to 85 years Exclusion Criteria: Proven or suspected prior episode of Clostridium difficile associated diarrhea. Unstable chronic medical condition or disease requiring significant change in therapy or hospitalization for worsening disease within 8 weeks before receipt of study vaccine. Any contraindication to vaccination or vaccine components, including previous anaphylactic reaction to any vaccine or vaccine-related components.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose of C. difficile vaccine<br> | Biological: Clostridium difficile vaccine<br>* 0.5 mL intramuscular injection on day 1, day 8, and day 30.<br>|
| Experimental: Low dose of C. difficile vaccine<br> | Biological: Clostridium difficile vaccine<br>* 0.5 mL intramuscular injection on day 1, day 8, and day 30.<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Placebo (0.9 percent saline) given as a 0.5 mL intramuscular injection on day 1, day 8, and day 30.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Reporting Prespecified Local Reactions Within 7 Days After Dose 1 (50- to 64-Year Age Cohort) | Pain at injection site: mild=does not interfere with activity; moderate=interferes with activity; severe=prevents daily activity; Grade 4=emergency department visit or hospitalization. Redness/swelling: Mild=2.5 to 5.0 cm; moderate= >5.0 to 10.0 cm; severe= >10 cm; Grade 4=necrosis or exfoliative dermatitis for redness category and only necrosis for swelling category. Any local reaction=any pain at the injection site, any swelling, or any redness. | From Day of Dose 1 vaccination to within 7 days after Dose 1 | 
| Percentage of Participants Reporting Prespecified Local Reactions Within 14 Days After Dose 2 (50- to 64-Year Age Cohort) | Pain at injection site: mild=does not interfere with activity; moderate=interferes with activity; severe=prevents daily activity; Grade 4=emergency department visit or hospitalization. Redness/swelling: Mild=2.5 to 5.0 cm; moderate= >5.0 to 10.0 cm; severe= >10 cm; Grade 4=necrosis or exfoliative dermatitis for redness category and only necrosis for swelling category. Any local reaction=any pain at the injection site, any swelling, or any redness. | From Day of Dose 2 vaccination to within 14 days after Dose 2 | 
| Percentage of Participants Reporting Prespecified Local Reactions Within 14 Days After Dose 3 (50- to 64-Year Age Cohort) | Pain at injection site: mild=does not interfere with activity; moderate=interferes with activity; severe=prevents daily activity; Grade 4=emergency department visit or hospitalization. Redness/swelling: Mild=2.5 to 5.0 cm; moderate= >5.0 to 10.0 cm; severe= >10 cm; Grade 4=necrosis or exfoliative dermatitis for redness category and only necrosis for swelling category. Any local reaction=any pain at the injection site, any swelling, or any redness. | From Day of Dose 3 vaccination to within 14 days after Dose 3 | 
| Percentage of Participants Reporting Systemic Events Within 7 Days After Dose 1 (50- to 64-Year Age Cohort) | Fever=temperature ≥38.0°C (100.4°C): Mild=38.0°C to 38.4°C (100.4°F-101.1°F); moderate=38.5°C to 38.9°C (101.2°F-102.0°F); severe=39.0°C to 40.0°C (102.1°F-104.0°F); Grade 4= >40.0°C (>104.0°F). Vomiting: Mild=1 to 2 times in 24 hours; moderate= >2 times in 24 hours; severe=requires intravenous hydration; Grade 4=emergency department visit or hospitalization for hypotensive shock. Diarrhea: Mild=2 to 3 loose stools in 24 hours; moderate=4 to 5 loose stools in 24 hours; severe= ≥6 loose stools in 24 hours; Grade 4=emergency department visit or hospitalization. Headache, fatigue, new or worsening joint or muscle pain: Mild=no interference with activity; moderate=some interference with activity; severe=significant interference with activity, prevents daily activity; Grade 4=emergency department visit or hospitalization. Any systemic event: Fever ≥38.0°C, vomiting, diarrhea, headache, fatigue, or new or worsening muscle or joint pain. | From Day of Dose 1 vaccination to within 7 days of Dose 1 | 
| Percentage of Participants With A Systemic Event Within 14 Days of Dose 2 (50- to 64-Year Age Cohort) | Fever=temperature ≥38.0°C (100.4°C): Mild=38.0°C to 38.4°C (100.4°F-101.1°F); moderate=38.5°C to 38.9°C (101.2°F-102.0°F); severe=39.0°C to 40.0°C (102.1°F-104.0°F); Grade 4= >40.0°C (>104.0°F). Vomiting: Mild=1 to 2 times in 24 hours; moderate= >2 times in 24 hours; severe=requires intravenous hydration; Grade 4=emergency department visit or hospitalization for hypotensive shock. Diarrhea: Mild=2 to 3 loose stools in 24 hours; moderate=4 to 5 loose stools in 24 hours; severe= ≥6 loose stools in 24 hours; Grade 4=emergency department visit or hospitalization. Headache, fatigue, new or worsening joint or muscle pain: Mild=no interference with activity; moderate=some interference with activity; severe=significant interference with activity, prevents daily activity; Grade 4=emergency department visit or hospitalization. Any systemic event: Fever ≥38.0°C, vomiting, diarrhea, headache, fatigue, or new or worsening muscle or joint pain. | From Day of Dose 2 vaccination to within 14 days after Dose 2 | 
| Percentage of Participants Reporting Systemic Events Within 14 Days After Dose 3 (50- to 64-Year Age Cohort) | Fever=temperature ≥38.0°C (100.4°C): Mild=38.0°C to 38.4°C (100.4°F-101.1°F); moderate=38.5°C to 38.9°C (101.2°F-102.0°F); severe=39.0°C to 40.0°C (102.1°F-104.0°F); Grade 4= >40.0°C (>104.0°F). Vomiting: Mild=1 to 2 times in 24 hours; moderate= >2 times in 24 hours; severe=requires intravenous hydration; Grade 4=emergency department visit or hospitalization for hypotensive shock. Diarrhea: Mild=2 to 3 loose stools in 24 hours; moderate=4 to 5 loose stools in 24 hours; severe= ≥6 loose stools in 24 hours; Grade 4=emergency department visit or hospitalization. Headache, fatigue, new or worsening joint or muscle pain: Mild=no interference with activity; moderate=some interference with activity; severe=significant interference with activity, prevents daily activity; Grade 4=emergency department visit or hospitalization. Any systemic event: Fever ≥38.0°C, vomiting, diarrhea, headache, fatigue, or new or worsening muscle or joint pain. | From Day of Dose 3 vaccination to within 14 days after Dose 3 | 
| Percentage of Participants Reporting Adverse Events (AEs) to Month 2 and Serious AEs (SAEs) to Month 13 (50- to 64-Year Age Cohort) | An AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death, persistent or significant disability/incapacity, or congenital anomaly/birth defect; is life-threatening; or requires or prolongs inpatient hospitalization. | AEs: From informed consent to Visit 6 (Month 2). SAEs: From informed consent to Visit 9 (Month 13) | 
| Percentage of Participants With A Local Reaction Within 7 Days of Dose 1 (65- to 85-Year Age Cohort) | Pain at injection site: mild=does not interfere with activity; moderate=interferes with activity; severe=prevents daily activity; Grade 4=emergency department visit or hospitalization. Redness/swelling: Mild=2.5 to 5.0 cm; moderate= >5.0 to 10.0 cm; severe= >10 cm; Grade 4=necrosis or exfoliative dermatitis for redness category and only necrosis for swelling category. Any local reaction=any pain at the injection site, any swelling, or any redness. | From Day of Dose 1 vaccination to within 7 days of Dose 1 | 
| Percentage of Participants With A Local Reaction Within 14 Days After Dose 2 (65- to 85-Year Age Cohort) | Pain at injection site: mild=does not interfere with activity; moderate=interferes with activity; severe=prevents daily activity; Grade 4=emergency department visit or hospitalization. Redness/swelling: Mild=2.5 to 5.0 cm; moderate= >5.0 to 10.0 cm; severe= >10 cm; Grade 4=necrosis or exfoliative dermatitis for redness category and only necrosis for swelling category. Any local reaction=any pain at the injection site, any swelling, or any redness. | From Day of Dose 2 vaccination to 14 days after Dose 2 | 
| Percentage of Participants With A Local Reaction Within 14 Days After Dose 3 (65- to 85-Year Age Cohort) | Pain at injection site: mild=does not interfere with activity; moderate=interferes with activity; severe=prevents daily activity; Grade 4=emergency department visit or hospitalization. Redness/swelling: Mild=2.5 to 5.0 cm; moderate= >5.0 to 10.0 cm; severe= >10 cm; Grade 4=necrosis or exfoliative dermatitis for redness category and only necrosis for swelling category. Any local reaction=any pain at the injection site, any swelling, or any redness. | From Day of Dose 3 vaccination to 14 days after Dose 3 | 
| Percentage of Participants With A Systemic Event Within 7 Days of Dose 1 (65- to 85-Year Age Cohort) | Fever=temperature ≥38.0°C (100.4°C): Mild=38.0°C to 38.4°C (100.4°F-101.1°F); moderate=38.5°C to 38.9°C (101.2°F-102.0°F); severe=39.0°C to 40.0°C (102.1°F-104.0°F); Grade 4= >40.0°C (>104.0°F). Vomiting: Mild=1 to 2 times in 24 hours; moderate= >2 times in 24 hours; severe=requires intravenous hydration; Grade 4=emergency department visit or hospitalization for hypotensive shock. Diarrhea: Mild=2 to 3 loose stools in 24 hours; moderate=4 to 5 loose stools in 24 hours; severe= ≥6 loose stools in 24 hours; Grade 4=emergency department visit or hospitalization. Headache, fatigue, new or worsening joint or muscle pain: Mild=no interference with activity; moderate=some interference with activity; severe=significant interference with activity, prevents daily activity; Grade 4=emergency department visit or hospitalization. Any systemic event: Fever ≥38.0°C, vomiting, diarrhea, headache, fatigue, or new or worsening muscle or joint pain. | From Day of Dose 1 vaccination to within 7 days of Dose 1 | 
| Percentage of Participants With a Systemic Event Within 14 Days of Dose 2 (65- to 85-Year Age Cohort) | Fever=temperature ≥38.0°C (100.4°C): Mild=38.0°C to 38.4°C (100.4°F-101.1°F); moderate=38.5°C to 38.9°C (101.2°F-102.0°F); severe=39.0°C to 40.0°C (102.1°F-104.0°F); Grade 4= >40.0°C (>104.0°F). Vomiting: Mild=1 to 2 times in 24 hours; moderate= >2 times in 24 hours; severe=requires intravenous hydration; Grade 4=emergency department visit or hospitalization for hypotensive shock. Diarrhea: Mild=2 to 3 loose stools in 24 hours; moderate=4 to 5 loose stools in 24 hours; severe= ≥6 loose stools in 24 hours; Grade 4=emergency department visit or hospitalization. Headache, fatigue, new or worsening joint or muscle pain: Mild=no interference with activity; moderate=some interference with activity; severe=significant interference with activity, prevents daily activity; Grade 4=emergency department visit or hospitalization. Any systemic event: Fever ≥38.0°C, vomiting, diarrhea, headache, fatigue, or new or worsening muscle or joint pain. | From Day of Dose 2 vaccination to within 14 days after Dose 2 | 
| Percentage of Participants Reporting Systemic Events Within 14 Days After Dose 3 (65- to 85-Year Age Cohort) | Fever=temperature ≥38.0°C (100.4°C): Mild=38.0°C to 38.4°C (100.4°F-101.1°F); moderate=38.5°C to 38.9°C (101.2°F-102.0°F); severe=39.0°C to 40.0°C (102.1°F-104.0°F); Grade 4= >40.0°C (>104.0°F). Vomiting: Mild=1 to 2 times in 24 hours; moderate= >2 times in 24 hours; severe=requires intravenous hydration; Grade 4=emergency department visit or hospitalization for hypotensive shock. Diarrhea: Mild=2 to 3 loose stools in 24 hours; moderate=4 to 5 loose stools in 24 hours; severe= ≥6 loose stools in 24 hours; Grade 4=emergency department visit or hospitalization. Headache, fatigue, new or worsening joint or muscle pain: Mild=no interference with activity; moderate=some interference with activity; severe=significant interference with activity, prevents daily activity; Grade 4=emergency department visit or hospitalization. Any systemic event: Fever ≥38.0°C, vomiting, diarrhea, headache, fatigue, or new or worsening muscle or joint pain. | From Day of Dose 3 vaccination to within 14 days after Dose 3 | 
| Percentage of Participants Reporting Adverse Events (AEs) to Month 2 and Serious AEs (SAEs) to Month 13 (65- to 85-Year Age Cohort) | An AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death, persistent or significant disability/incapacity, or congenital anomaly/birth defect; is life-threatening; or requires or prolongs inpatient hospitalization. | AEs: From informed consent to Visit 6 (Month 2). SAEs: From informed consent to Visit 9 (Month 13) | 

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