There is No Association Between Patient Outcomes and Demographics in an Open-Label Safety and Efficacy Study of RBX2660, a Microbiota-Based Drug for Recurrent Clostridium difficile Infection

Arnab Ray MD, Gail Hecht MD, Robert Orenstein DO, Christine Lee MD, Erik R. Dubberke MD, MSPH, Sahil Khanna MBBS, Ken Blount PhD

Background

• Multiple microbiota therapeutics are currently in clinical development for preventing recurrent Clostridium difficile infection (rCDI) in multi-recurrent patients.
• As these therapies move closer to potential approval, it will be important to assess their broad utility among demographic groups.
• In a recent double-blind, placebo-controlled Phase 2B trial of RBX2660, a standardized microbiota-based drug, there were no differences in efficacy among key demographic designations.
• Herein, we evaluated data from a Phase 2 controlled open-label trial of RBX2660 to determine whether rCDI prevention differed in relationship to age, sex, or geographic region.

Methods

• Data analyzed were from a prospective, multicenter, open-label Phase 2 study (NCT02589847) consisting of an RBX2660 treatment arm and a historical control group.
• Key inclusion criteria: >18 years old with documentation of either 2 recurrences after a primary episode and has completed at least two rounds of standard-of-care oral antibiotic therapy, or at least 2 episodes of severe CDI resulting in hospitalization; a positive stool test for the presence of toxigenic C. difficile within 60 days prior to enrollment.
• Key exclusion criteria: History of inflammatory bowel disease (ulcerative colitis, Crohn’s disease or microscopic colitis), irritable bowel syndrome, chronic diarrhea, celiac disease, colostomy; evidence of active colitis; planned surgery that will require perioperative antibiotics within 6 months of treatment; compromised immune system (white blood cell count <1000 cells/μL).
• Antibiotics were discontinued 24-48 hours prior to administration of the first enema.
• Patients received up to 2 RBX2660 ddoses elivered via enema with doses 7 +/- 2 days apart.
• Safety was assessed via a patient diary: in clinic at 1, 4, and 8 weeks and via telephone at 2, 3, between 5-7 weeks, and at 3, 6, 12 and 24 months.
• Success was defined as the absence of CDI at 8 weeks following completion of the last treatment. Patients were classified as a treatment failure if all four (4) of the following criteria were met: recurrence of diarrhea less than 8 weeks after administration of the last assigned study enema, a positive laboratory diagnosis of C. difficile as conducted and reported by the study investigator, a need for retreatment for CDI, and no other cause for diarrhea.
• Pearson’s chi-square test or a Fisher’s exact test was used to compared the proportion of subjects in the treatment arm who were recurrence-free to the proportion of historical controls who were recurrence-free.

Results

• See poster (PDF 216 KB)

Conclusions

• The efficacy outcome of RBX2660 did not depend on sex, age, or region of the clinical trial center.
• RBX2660 demonstrates benefit across a broad patient population.