Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCH CD3-OLS)

Study Overview
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Brief Summary
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This is a prospective, multicenter, open-label Phase 3 study of a microbiota suspension of intestinal microbes. Patients who have had at least one recurrence of CDI after a primary episode and have completed at least one round 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. Subjects may receive a second RBX2660 enema if they are deemed treatment failures following the initial enema per the protocol-specified treatment failure definition.

Detailed Description
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This is a prospective, multicenter, open-label Phase 3 study of a microbiota suspension of intestinal microbes. The primary assessments for this study are (i) safety via assessment of treatment-emergent adverse events and (ii) efficacy of RBX2660 preventing recurrent episodes of CDI measured at 8 weeks after treatment. Follow-up office visits occur at 1 week and 8 weeks after completing the initial study treatment. Telephone assessments occur at 4 weeks, and 4 and 6 months after the study. Patients who have had at least one recurrence of CDI after a primary episode and have completed at least one round 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. Subjects may receive a second RBX2660 enema if they are deemed treatment failures following the initial enema per the protocol-specified treatment failure definition.

Official Title
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A Phase 3 Open-Label Clinical Study to Evaluate the Safety and Tolerability of Rebiotix RBX2660 (Microbiota Suspension) in Subjects With Recurrent Clostridium Difficile Infection

Conditions
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Clostridium Difficile Infection, Infection, Communicable Diseases

Intervention / Treatment
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* Drug: RBX2660


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years old. Medical record documentation of either: a) a current diagnosis or history of recurrent CDI as determined by the treating physician, b) or has had at least two episodes of severe CDI resulting in hospitalization. Is currently taking or was just prescribed antibiotics to control CDI related diarrhea at the time of enrollment. [Note: Subject's CDI diarrhea must be controlled (<3 unformed/loose stools/day) while taking antibiotics during screening.] Exclusion Criteria: Has continued CDI diarrhea despite being on a course of antibiotics prescribed for CDI treatment. Requires systemic antibiotic therapy for a condition other than CDI. Fecal microbiota transplant (FMT) within the past 6 months. FMT with an associated serious adverse event related to the FMT product or procedure. Bezlotoxumab (CDI monoclonal antibodies) if received within the last year. CD4 count <200/mm^3 during Screening. An absolute neutrophil count of <1000 cells/µL during Screening. Pregnant, breastfeeding, or intends to become pregnant during study participation.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>RBX2660 is an enema of a microbiota suspension | Drug: RBX2660<br>* RBX2660 is a microbiota suspension administered as an enema<br>* Other names: Microbiota suspension;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of RBX2660 in subjects with recurrent CDI. | Number of subjects with investigational product- and/or enema-related treatment-emergent adverse events (TEAEs). | Up to 6 months after last study treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of RBX2660 measured at 8 weeks after treatment. | The absence of C. difficile diarrhea without the need for retreatment through 8 weeks after administration of the study treatment. | 8 weeks after completing the study treatment | 
| Sustained clinical response through 6 months after treatment. | Treatment success of the presenting CDI recurrence and no new CDI episodes for greater than 8 weeks through 6 months after completing a study treatment assessed by subject phone interview up to 6 months after the last study treatment. | 6 months after completing the study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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C diff, CDI, FMT, C. Difficile Diarrhea, Clostridium Difficile, Fecal Microbiota Transplant, Microbiota Restoration Therapy, Diarrhea, Microbial Suspension, Fecal Transplant, C Difficile Colitis, Clostridium Difficile Associated Diarrhea, C diff diarrhea, C Difficile