Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection

Study Overview
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Brief Summary
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This is the first prospective, multi-center, double-blinded, randomized controlled study of a microbiota suspension derived from intestinal microbes. Patients who have had at least two recurrences of C. difficile infection (CDI) after a primary episode and have completed at least two rounds of standard-of-care oral antibiotic therapy or have had at least two episodes of severe CDI resulting in hospitalization may be eligible for the study. Patients whose CDI returns in less than 8 weeks after the last assigned study treatment may be eligible to receive up to 2 treatments with RBX2660 in the open-label portion of the study.

Detailed Description
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This is the first prospective, multi-center, double-blinded, randomized controlled study of a microbiota suspension derived from intestinal microbes. The primary assessments for this study are (i) efficacy of RBX2660 compared to placebo at 8 weeks and (ii) safety via assessment of adverse events. Study visits are at 1-, 4- and 8-weeks after treatment with additional follow-up at 3, 6 12 and 24 months post treatment. Patients who have had at least two recurrences of C. difficile infection (CDI) after a primary episode and have completed at least two rounds of standard-of-care oral antibiotic therapy or have had at least two episodes of severe CDI resulting in hospitalization may be eligible for the study. Patients whose CDI returns in less than 8 weeks after the last assigned study treatment may be eligible to receive up to 2 treatments with RBX2660 in the open-label portion of the study.

Official Title
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A Phase 2B Prospective, Randomized, Double-blinded, Placebo-controlled Clinical Study Demonstrating the Efficacy and Safety of Rebiotix RBX2660 (Microbiota Suspension) for the Treatment of Recurrent Clostridium Difficile Infection

Conditions
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Enterocolitis Clostridium Difficile Recurrent

Intervention / Treatment
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* Biological: RBX2660 (microbiota suspension)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years Medical record documentation of recurrent CDI either: a) at least two recurrences after a primary episode and has completed at least two rounds of standard-of-care oral antibiotic therapy or b) has had at least two episodes of severe CDI resulting in hospitalization. Documented history that the subject's recurrent CDI is controlled while on antibiotics even if the subject is not currently on antibiotics. A positive stool test for the presence of C. difficile within 60 days prior to enrollment. Exclusion Criteria: A known history of continued C. difficile diarrhea while taking on a course of antibiotics prescribed for CDI treatment. Requires antibiotic therapy for a condition other than recurrent CDI. Previous fecal transplant prior to study enrollment. History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis. History of irritable bowel syndrome (IBS). History of chronic diarrhea. History of celiac disease. Colostomy. Planned surgery requiring perioperative antibiotics within 6 months of study enrollment. Life expectancy of < 12 months. Compromised immune system.

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>Two enemas of RBX2660 (microbiota suspension) administered 7 days apart | Biological: RBX2660 (microbiota suspension)<br>* A suspension of intestinal microbes<br>|
| Placebo Comparator: Group B<br>Two enemas of placebo administered 7 days apart | Other: Placebo<br>* A suspension of saline and cryoprotectant<br>|
| Active Comparator: Group C<br>1 enema of RBX2660 (microbiota suspension) and 1 enema of placebo administered 7 days apart | Biological: RBX2660 (microbiota suspension)<br>* A suspension of intestinal microbes<br>Other: Placebo<br>* A suspension of saline and cryoprotectant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Success of Group A (2 Doses of RBX2660) vs Group B (2 Doses of Placebo) (ITT) | The primary endpoint is to evaluate treatment success, defined as the absence of CDAD without the need for retreatment with C. difficile anti-infective therapy or fecal transplant (FT) at 56 days after administration of the last assigned study enema, of Group A (two enemas of RBX2660) vs. Group B (two enemas of placebo). | 8 weeks after last assigned study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Success Between Group C (1 Enema of RBX2660 and 1 Enema of Placebo) vs Group B (Two Enemas of Placebo) (ITT) | Treatment Success was defined as the absence of CDAD without the need for retreatment with C. difficile anti-infective therapy or fecal transplant (FT) at 56 days after administration of the last assigned study enema | 8-weeks | 
| Treatment Success Evaluated Between Group A (Two Enemas of RBX2660) Versus Group C (1 Enema of RBX2660 and 1 Enema of Placebo) (ITT) | Treatment success, defined as the absence of CDAD without the need for retreatment with C. difficile anti-infective therapy or fecal transplant (FT) at 56 days after administration of the last assigned study enema. | 8-weeks | 
| SF-36 Scores Obtained at the 1-week, 4-week, and 8-week Assessments Visits During the Double-blind Period as Compared to Baseline (ITT) | The validated SF-36 scale was used to identify changes to quality of life (QoL) following study treatment. Each component is analyzed on a norm-based scoring (0-100) with a higher score representing an improvement in QoL. | 8-week | 
| Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group A vs. Group B (ITT) | Time to CDI Recurrence was evaluated using Kaplan-Meier Analysis and expressed by percentage of subjects who were recurrence free at a certain time point (every 7 days) from completion of the last blinded enema. | 8-weeks | 
| Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group C vs. Group B (ITT) | Time to CDI Recurrence was evaluated using Kaplan-Meier Analysis and expressed by percentage of subjects who were recurrence free at a certain time point (every 7 days) from completion of the last blinded enema. | 8-weeks | 
| Time to CDAD Recurrence After Completion of the Assigned Study Treatment for Group A vs. Group C (ITT) | Time to CDI Recurrence was evaluated using Kaplan-Meier Analysis and expressed by percentage of subjects who were recurrence free at a certain time point (every 7 days) from completion of the last blinded enema. | 8-weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clostridium difficile, CDI, CDAD, Fecal transplant, Fecal Microbiota Transplant, Diarrhea, FMT, Microbiota restoration therapy, Microbiota suspension, Fecal bacteriotherapy, C diff diarrhea, C diff