Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD3)

Rebiotix

Status and phase: Completed; Phase 3

Conditions: Clostridium Difficile Infection (CDI)

Treatments: Drug: Placebo; Drug: RBX2660; Drug: Open label RBX2660 (only for confirmed CDI recurrence)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03244644

2017-01

Details and patient eligibility

About

This is a prospective, multicenter, randomized, double-blinded, placebo-controlled Phase 3 study of a microbiota suspension of intestinal microbes. Patients who have had at least one recurrence 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 Clostridioides difficile infection (CDI) resulting in hospitalization within the last year may be eligible for the study. Subjects who are deemed failures following the blinded treatment per the pre-specified treatment failure definition may elect to receive an unblinded dose of RBX2660.

Full description

This is a prospective, multicenter, randomized, double-blinded, placebo-controlled Phase 3 study of a microbiota suspension of intestinal microbes. The primary assessments for this study are (i) efficacy of RBX2660 as compared to a Placebo in preventing recurrent episodes of CDI and (ii) safety via assessment of adverse events. The primary efficacy analysis of the study will be a Bayesian hierarchical model, which formally incorporates data from a previous randomized Phase 2b study (Protocol 2014-01, NCT02299570) of RBX2660.

Follow-up office visits occur at weeks 1-, 4- and 8 after completing the blinded study treatment. Telephone assessments for adverse events occur during weeks 2, 3 and 6 after the study treatment and at months 3 and 6. Patients who have had at least one recurrence 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 within the last year may be eligible for the study. Study Subjects who are deemed failures following the blinded treatment per the pre-specified treatment failure definition may elect to receive an unblinded dose of RBX2660.

Enrollment: 320 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. ≥ 18 years old.
2. Medical record documentation of recurrent CDI per the study definition, that includes either: a) at least one recurrence after a primary episode and has completed at least one round of standard-of-care oral antibiotic therapy or b) has had at least two episodes of severe CDI resulting in hospitalization within the last year.
3. A positive stool test for the presence of toxigenic C. difficile within 30 days prior to or on the date of enrollment.
4. 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 this course of antibiotics]

Exclusion criteria

1. Currently has continued CDI diarrhea despite being on antibiotics prescribed for CDI treatment.
2. Previous fecal transplant
3. History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn's disease, or microscopic colitis.
4. Diagnosis of irritable bowel syndrome (IBS) as determined by Rome III criteria.
5. Compromised immune system (e.g. immunosuppressed due to a medical condition or medication; current or recent (< 90 days) treatment with chemotherapy)
6. An absolute neutrophil count of <1000 cells/µL during screening.
7. Pregnant, breastfeeding, or intends to become pregnant during study participation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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320 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo is an suspension of normal saline. Packaging and labeling are identical to the packaging and labeling for RBX2660 to support the study blinding

Treatment:

Drug: Open label RBX2660 (only for confirmed CDI recurrence)

Drug: Placebo

RBX2660

Experimental group

Description:

RBX2660 is a rectally administered microbiota suspension in a 0.9% sodium chloride irrigation United States Pharmacopeia (USP) solution and cryoprotectant

Treatment:

Drug: Open label RBX2660 (only for confirmed CDI recurrence)

Drug: RBX2660