Dale Gerding, MD, Courtney Jones, BS, Ken Blount, PhD, Bill Shannon, PhD MBA
- Recurrent Clostridium difficile infections (rCDI) has been recognized as an urgent health threat.
- Numerous therapeutics are being developed to reduce recurrence and have been evaluated in clinical trials.
- RBX2660 is a standardized microbiota-based drug manufactured from live human-derived microbes and was evaluated in PUNCH CD 2, a randomized, placebo-controlled Phase 2b trial for rCDI.
- Twenty (20) PUNCH CD 2 patients in the placebo arm met response criteria of no CDI recurrence within 8 weeks.
- To contextualize this placebo response observation, we conducted a meta-analysis of response rates among placebo-treated patients in additional rCDI trials.
- Five (5) blinded, randomized, and placebo-controlled trials were included in this meta-analysis 1-5.
- Studies required patients to have ≥15 or >21-4 prior CDI recurrences.
- All patients completed standard-of-care antibiotic course prior to experimental treatment.
- Four (4) studies tested a vehicle placebo administered by the same route as the active treatment (oral, intravenous, or enema) 1,2,4,5, and 1 study tested an autologous fecal transplant administered via enema.
- Response to treatment was defined as no CDI recurrence within 8-12 weeks.
- The proportional response rates with 95% confidence interval were calculated and compared in aggregate and among studies.
- A total of 154 of 292 placebo-treated patients (53%) met study specific response criteria.
- Placebo response rates ranged from 43%-58%.
- No study group presented a significantly different outcome from the aggregate cohort.
- No correlation of response with placebo administration route was observed.
- This meta-analysis demonstrates that response rates for blinded placebo-treated patients are consistent among 5 trials of experimental rCDI therapeutics, including a phase 2B trial of RBX2660.
- This analysis provides a useful framework for interpreting published rCDI trials, and for designing and interpreting future rCDI therapeutics trials.
- Further evaluation of placebo response in rCDI patients is warranted.
- Dubberke E et al. Presented at Infectious Diseases Week 2016, New Orleans, LA.
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