Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (PUNCHCD3)
Summary
This is a prospective, multicenter, randomized, double-blinded, placebo-controlled Phase 3 study of a microbiota suspension of intestinal microbes. Patients who have had at least one recurrence after a primary episode and have completed at least one round of standard-of-care oral antibiotic therapy or have had at least two episodes of severe Clostridioides difficile infection (CDI) resulting in hospitalization within the last year may be eligible for the study. Subjects who are deemed failures following the blinded treatment per the pre-specified treatment failure definition may elect to receive an unblinded dose of RBX2660.
Timeline
- Start
- 2017-07-31
- Primary completion
- 2020-04-02
- Completion
- 2020-08-03
Outcome
Met primary endpoint
paper the model-estimated treatment success rate was 70.6% with RBX2660 versus 57.5% with placebo PMID 36287379 ↗
registry analysis (superiority test); Placebo vs RBX2660; Treatment Difference 13.1 (95% CI 2.3 to 24.0) NCT03244644 ↗
release “Ferring Pharmaceuticals and Rebiotix, a Ferring Company, today presented results from the pivotal Phase 3 PUNCH™ CD3 clinical trial, demonstrating superior efficacy” ferring.com ↗
release “RBX2660 pivotal Phase 3 trial successfully met the primary endpoint” ferring.com ↗
Publications
- Background Bakken JS. Feces transplantation for recurrent Clostridium difficile infection: US experience and recommendations. Microb Ecol Health Dis. 2015 May 29;26:27657. doi: 10.3402/mehd.v26.27657. eCollection 2015. No abstract available.
- Background EISEMAN B, SILEN W, BASCOM GS, KAUVAR AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958 Nov;44(5):854-9. No abstract available.
- Background Miller MA, Louie T, Mullane K, Weiss K, Lentnek A, Golan Y, Kean Y, Sears P. Derivation and validation of a simple clinical bedside score (ATLAS) for Clostridium difficile infection which predicts response to therapy. BMC Infect Dis. 2013 Mar 25;13:148. doi: 10.1186/1471-2334-13-148.
- Chopra T, Van Handel D, Baggott B, Orenstein R, Reveles K, Guthmueller B, Srivastava S, Khanna S. Efficacy Outcomes of Fecal Microbiota, Live-jslm in Preventing Recurrent Clostridioides difficile Infection from Seven Clinical Studies. Infect Dis Ther. 2026 Aug;15(8):2071-2086. doi: 10.1007/s40121-026-01374-9. Epub 2026 Jun 12.
- Lee C, Feuerstadt P, Louie T, Bancke L, Guthmueller B, Harvey A, Hoeyer F, Orenstein R, Dubberke ER, Khanna S. Integrated analysis of the safety of fecal microbiota, live-jslm in adults with recurrent Clostridioides difficile infection from five prospective clinical trials: an update. Ther Adv Gastroenterol. 2025 Nov 12;18:17562848251395566. doi: 10.1177/17562848251395566. eCollection 2025.
- Mishra R, Harvey A, Guo A, Tillotson G, Feuerstadt P, Khanna S, Shannon WD, Blount KF. Microbiome and metabolome changes after fecal microbiota, live-jslm, administration are associated with health-related quality of life improvements. Anaerobe. 2025 Dec;96:103006. doi: 10.1016/j.anaerobe.2025.103006. Epub 2025 Oct 18.
- Adamowicz E, Kraft CS, Ward T, Mehta N, Shannon WD, Mishra R, Blount KF. Decreased Antimicrobial Resistance Gene Richness Following Fecal Microbiota, Live-jslm (REBYOTA(R)) Administration: Post Hoc Analysis of PUNCH CD3. Open Forum Infect Dis. 2025 Jul 2;12(7):ofaf382. doi: 10.1093/ofid/ofaf382. eCollection 2025 Jul.
- Claypool J, Lindved G, Myers PN, Ward T, Nielsen HB, Blount KF. Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infection. Gut Microbes. 2025 Dec;17(1):2520412. doi: 10.1080/19490976.2025.2520412. Epub 2025 Jun 24.
- Blount KF, Papazyan R, Ferdyan N, Srinivasan K, Gonzalez C, Shannon WD, Fuchs BC. Microbiome and Metabolome Restoration After Administration of Fecal Microbiota, Live-jslm (REBYOTA) for Preventing Recurrent Clostridioides difficile Infection. J Infect Dis. 2025 Jul 11;231(6):e1022-e1033. doi: 10.1093/infdis/jiae418.
- Feuerstadt P, Allegretti JR, Dubberke ER, Guo A, Harvey A, Yang M, Garcia-Horton V, Fillbrunn M, Tillotson G, Bancke LL, LaPlante K, Garey KW, Khanna S. Efficacy and Health-Related Quality of Life Impact of Fecal Microbiota, Live-jslm: A Post Hoc Analysis of PUNCH CD3 Patients at First Recurrence of Clostridioides difficile Infection. Infect Dis Ther. 2024 Jan;13(1):221-236. doi: 10.1007/s40121-023-00907-w. Epub 2024 Jan 18.
- Garey KW, Dubberke ER, Guo A, Harvey A, Yang M, Garcia-Horton V, Fillbrunn M, Wang H, Tillotson GS, Bancke LL, Feuerstadt P. Effect of Fecal Microbiota, Live-Jslm (REBYOTA [RBL]) on Health-Related Quality of Life in Patients With Recurrent Clostridioides difficile Infection: Results From the PUNCH CD3 Clinical Trial. Open Forum Infect Dis. 2023 Jul 20;10(8):ofad383. doi: 10.1093/ofid/ofad383. eCollection 2023 Aug.
- Khanna S, Assi M, Lee C, Yoho D, Louie T, Knapple W, Aguilar H, Garcia-Diaz J, Wang GP, Berry SM, Marion J, Su X, Braun T, Bancke L, Feuerstadt P. Efficacy and Safety of RBX2660 in PUNCH CD3, a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial with a Bayesian Primary Analysis for the Prevention of Recurrent Clostridioides difficile Infection. Drugs. 2022 Oct;82(15):1527-1538. doi: 10.1007/s40265-022-01797-x. Epub 2022 Oct 26.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | RBX2660 | Other / unclassified | — | Rectal |