Meta-Analysis of Response Rates Among Placebo-Treated Patients from Five Clinical Trials of Experimental Recurrent Clostridium difficile Therapeutics

Dale Gerding, MD, Courtney Jones, BS, Ken Blount, PhD, Bill Shannon, PhD MBA

Meta-Analysis of Response Rates Among Placebo-Treated Patients from Five Clinical Trials of Experimental Recurrent Clostridium difficile Therapeutics Poster Image

Download this poster (174 KB)
Download the abstract (91 KB)

ASM Microbe 2017
June 1-5, 2017, New Orleans, LA

Background

  • 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.

Methods

  • 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.

Results

  • 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.

Conclusions

  • 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.

References

  1. Dubberke E et al. Presented at Infectious Diseases Week 2016, New Orleans, LA.
  2. Seres Therapeutics [news release]. Cambridge, MA: Seres Therapeutics, Inc. communication; July 29, 2016. http://ir.serestherapeutics.com/phoenix.zhtml?c=254006&p=irol-newsArticle&ID=2240833. Accessed May 16, 2017.
  3. Kelly CR et al. Ann Intern Med. 2016:165:609-616.
  4. Wilcox MH et al. N Engl J Med. 2017;376:305-317.
  5. Surawicz CM et al.Clin Infect Dis. 2000;31:1012–7.