Safety and Efficacy Study of VP20621 for Prevention of Recurrent Clostridium Difficile Infection

Study Overview
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Brief Summary
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The objectives of this study are: (1) to evaluate the safety and tolerability of VP 20621 dosed orally for up to 14 days in adults previously treated for CDI; (2) to characterize the frequency and duration of stool colonization with the VP 20621 strain of C. difficile; (3) to evaluate the efficacy of VP 20621 for prevention of recurrence of CDI; and (4)to select a dose regimen of VP 20621 to be used in future studies.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Assess the Safety and Efficacy of VP 20621 for Prevention of Recurrence of Clostridium Difficile Infection (CDI) in Adults Previously Treated for CDI

Conditions
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Clostridium Difficile Infection

Intervention / Treatment
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* Biological: VP20621
* Biological: VP20621
* Other: Placebo
* Biological: VP20621


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subjects, 18 years of age and over, who understand the risks and benefits of participation and have provided written informed consent for the study. Subjects who are experiencing a first event or first recurrence of clostridium difficile (CDI) within the last 28 days and have been successfully treated with an antibiotic for CDI. Subjects who are medically stable. Subjects who are willing and able to comply with the study procedures and visit schedules outlined. If female be post-menopausal, surgically sterile or agree to follow an acceptable method of birth control. Exclusion Criteria: Subjects who have had more than 2 episodes of CDI within the last 6 months. Subjects who have been diagnosed with Inflammatory Bowel Disease,active Irritable Bowel Syndrome, celiac disease, active gastroparesis, toxic megacolon. GI surgery within 6 weeks before the day of randomization Have known immunodeficiency disorder, such as HIV Infection Pregnant or breast feeding females. Concurrent acute life-threatening diseases. Inability to tolerate oral liquids. Have an absolute neutrophil count < 1000/mm3 at screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* 10 mL placebo once daily for 14 days<br>|
| Experimental: VP20621 Low Dose and Placebo<br> | Biological: VP20621<br>* VP20621 as oral liquid once daily for 7 days followed by placebo as oral liquid once daily for seven days<br>Other: Placebo<br>* 10 mL placebo once daily for 14 days<br>|
| Experimental: VP20621 High Dose and Placebo<br> | Biological: VP20621<br>* VP20621 as oral liquid once daily for 7 days followed by placebo as oral liquid once daily for 7 days<br>Other: Placebo<br>* 10 mL placebo once daily for 14 days<br>|
| Experimental: VP20621 High Dose<br> | Biological: VP20621<br>* VP20621 as oral liquid once daily for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An adverse event (AE) is any untoward, undesired, unplanned clinical event in the form of signs, symptoms, disease, or laboratory or physiological observations occurring in a study participant, regardless of causal relationship. TEAEs were defined as all AEs that start during the study drug treatment period (and up to 7 days after the last dose of the study drug) and were not seen at baseline, or were seen at baseline but increased in frequency and/or severity during the study drug treatment period (and up to 7 days after the last dose of study drug). SAE was any AE that results in any of the following outcomes: death, a life-threatening event, inpatient hospitalization or prolongation of an existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, other medically important events based upon appropriate medical judgement. | Baseline up to 7 days after the last dose of study drug (up to Week 3) | 
| Number of Participants With Positive Clostridium Difficile Stool Cultures Demonstrating Non-Toxigenic Clostridium Difficile-Strain M3 |  | After study drug administration period (14 days) through Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clostridium Difficile Infection (CDI) Recurrence | CDI recurrence was defined as at least 1 event characterized by ALL of the following: >=3 unformed (loose or watery) stools within 24 hours (data derived from Diarrhea case report form (CRF) page which was to be completed for any clinical event of diarrhea or loose/watery stool occurring between Day 1 and Week 6); a positive C. difficile stool assay, or pseudomembranes on endoscopy/surgery; and no other likely cause of the diarrhea in the opinion of the investigator. | Baseline (Day 1) up to Week 6 | 
| Number of Participants With Use of Antibacterial Treatment for CDI | Any antibacterial medication used after Day 1 for which the investigator selected the indication antibacterial for C. difficile infection. | Baseline (Day 1) up to Week 6 | 
| Number of Participants With Clinical Events of Diarrhea or Loose/Watery Stools | Data were derived from all AEs starting on or after Day 1 for which a Diarrhea CRF page was completed. | Baseline (Day 1) up to Week 6 | 
| Time to First CDI Recurrence | CDI recurrence was defined as at least 1 event characterized by ALL of the following: >=3 unformed (loose or watery) stools within 24 hours (data derived from Diarrhea CRF page which was to be completed for any clinical event of diarrhea or loose/watery stool occurring between Day 1 and Week 6); a positive C. difficile stool assay, or pseudomembranes on endoscopy/surgery; and no other likely cause of the diarrhea in the opinion of the investigator. Time of onset is from date of randomization to date of first CDI recurrence. Time to first CDI recurrence was assessed using Kaplan-Meier curve. Due to small number of subjects (<50%) with CDI recurrence, median time to event was not evaluable. | Baseline (Day 1) up to Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diarrhea, Clostridium difficile, Clostridium infections, Signs and Symptoms Digestive, Bacterial Infections, Pharmacologic Actions