Mayur Ramesh, MD; Sahil Khanna, MBBS, MS; Julie Messer, BS; Matt Adams, MS
- Antibiotic exposure is a major risk factor for the development of Clostridium difficile infection (CDI).
- Antibiotic treatment of CDI with standard of care antibiotics contributes to persistent disruption of the intestinal microbiota and predisposes to recurrent infection. The risk of recurrence increases following a second episode.
- Microbiota-based drugs have shown promise in durable prevention of CDI recurrence.
- RBX2660, a microbiota-based drug manufactured from live human-derived microbes, is under study for the prevention of recurrent CDI.
- We report on the durability of RBX2660 in a post-hoc analysis of PUNCH CD 2, a Phase 2b randomized, double-blinded, placebo-controlled trial.
- Patients with recurrent CDI enrolled in the three-arm PUNCH CD 2 trial were randomized 1:1:1 to receive either: 2 doses of RBX2660, (Group A); 2 doses of placebo (Group B); or 1 dose of RBX2660 and 1 dose of placebo (Group C) via enema with doses 7 days apart (Figure 1).
- Failures in any study group were eligible to receive open-label treatment with up to 2 doses of RBX2660.
- Success was measured as the absence of CDI symptoms at 8 weeks post treatment.
- Failure was defined as: the presence of diarrhea, with or without other CDI symptoms, at less than 8 weeks after last treatment; a positive stool test for C. difficile; the need for retreatment for CDI and no other cause for diarrhea was identified (all four criteria were required).
- Safety follow-ups were scheduled in clinic at 1, 4 and 8 weeks and via telephone at 2, 3 and 5-7 weeks and at 3, 6, 12, and 24 months. Durability assessments occurred concurrently and are on-going until 24 months.
Major Inclusion Criteria
- Age ≥ 18 years old
- A positive stool test for Clostridium difficile within 60 days prior to enrollment
- At least two recurrences of CDI after a primary episode
- At least two episodes of severe CDI resulting in hospitalization
Major Exclusion Criteria
- History of inflammatory bowel disease (ulcerative colitis, Crohn’s disease or microscopic colitis); irritable bowel syndrome; chronic diarrhea; celiac disease
- Evidence of active colitis
- Known exposure to antibiotics within 6 months after study enrollment
- Compromised immune system
- White blood cell count <1000 cells/μL
- A total of 107 patients (median age 63, range: 18-92 years; 59.8% female) at 21 centers in the U.S. and Canada received at least 1 dose of RBX2660 (Table 1).
- Group A (n=41) and Group C (n=42)
- Placebo patients who went on to receive open-label RBX2660 (n=24)
- The overall success rate of patients who received at least one dose of RBX2660 in the blinded and open-label phases of the trial was 88.8% (95/107) (Table 1).
- Of the successful patients, 4.2% (4/95) developed a new episode of CDI confirmed by a positive test > 8 weeks after the last RBX2660 treatment (Table 2).
- The long-term CDI-free rate (median follow-up: 8.3 months; range 1.6 to 14.9 months) was 95.8% (91/95) (Table 3).
- RBX2660, a microbiota-based drug, provided a durable cure for recurrent CDI in a randomized, double-blinded, placebo-controlled trial with up to 12-months follow-up. Long-term follow-up to 24 months is ongoing.
- Longitudinal assessment of the impact of RBX2660 treatment on the intestinal microbiota of patients may provide additional insight into durable prevention of CDI.