Prevention of Recurrent Clostridium difficile at Six Months Following Treatment with Microbiota-based Therapy RBX2660: Durability Results From a Phase 2 Open-label Study

Sarah Mische PhD, Robert Orenstein DO, Erik R. Dubberke MD, Sahil Khanna MBBS, Gail Hecht MD, Herbert Dupont MD, Christine H. Lee MD, Dale N. Gerding MD, Ken Blount PhD

Background

• Effective treatment options for recurrent C. difficile infection (rCDI) are limited.
• High recurrence rates are associated with current standard-of-care antibiotic therapy.
• Microbiota-based therapies are being developed and evaluated in clinical studies.
• RBX2660 has shown efficacy in preventing rCDI at 8 weeks in a randomized, blinded, placebo-controlled Phase 2B trial (PUNCH CD2; NCT02299570).
• Here we report RBX2660 durability beyond the initial primary clinical end-point of a subsequent Phase 2 openlabel study (NCT02589847), demonstrating rCDI prevention at 6 months post-treatment.

Clinical Trial Design

• Inclusion criteria: >18 years old with documentation of either 2 recurrences after a primary episode and had 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.
• Antibiotics were discontinued 24-48 hours prior to the first enema.
• Safety was assessed 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 last treatment. Subjects were classified as treatment failures if all 4 criteria were met (recurrence of diarrhea <8 weeks after delivery of treatment, positive laboratory C. difficile diagnosis, requirement of retreatment and no other cause for diarrhea).

Demographics

• See poster (2.5 MB)

RBX2660 Safety

• See poster (2.5 MB)

RBX2660 Efficacy

6 month follow-up

• 6-month efficacy data collected for 117 of 119 patients who had successful response to RBX2660 at 8-weeks post-treatment
• 8 exits due to non-CDI reasons: Lost to follow-up, death
• 3 patients reported CDI recurrence
• 97.2% of subjects who had successful outcome at 8 weeks remained CDI-free at 6 months post-RBX2660

Conclusion

• RBX2660 was efficacious for the prevention of rCDI with long-term durability at 6 months post-treatment.
• This result is consistent with 6 month rCDI prevention reported for the Phase 2B PUNCH CD2 study.
• Long-term follow-up of RBX2660 safety and efficacy 24 months is ongoing.