Final Results from a Phase 2b Randomized, Placebo-Controlled Clinical Trial of RBX2660: A Microbiota-Based Drug for the Prevention of Recurrent Clostridioides difficile Infection

Abstract

Introduction: Effective treatments for recurrent Clostridioides difficile infection (rCDI) are urgently needed. RBX2660 is an investigational microbiota-based live biotherapeutic to reduce CDI recurrence following standard-of-care antibiotic treatment in individuals with rCDI.Here we report the final safety data through 24 months of follow-up as well as final efficacy data, reflecting alignment of the pre-specified statistical analysis plan definitions with the data presented. Methods: The PUNCH CD2 clinical trial was a prospective, multicenter, randomized, doubleblinded, placebo-controlled, three-arm phase 2b

Safety of fecal microbiota, live-jslm (REBYOTA™) in individuals with recurrent Clostridioides difficile infection: data from five prospective clinical trials

“…Safety data from five prospective trials were combined (three phase II and two phase III; Figure 1(a) and Supplemental Table 1). 25,26,29 These trials had similar protocols and evaluated the same product that was generated using standardized manufacturing practices and iteratively evolving pathogen screening to help ensure product safety. All trials are complete except for one ongoing trial (PUNCH CD3-OLS); data from participants enrolled into that trial between 30 July 2019 and 25 March 2022 were incorporated into this analysis.…”

“…RBL is manufactured according to good manufacturing practices and undergoes standardized screening procedures and pathogen testing in alignment with FDA requirements to help ensure patient safety. 25 The efficacy and safety of RBL has been assessed in five prospective clinical trials comprising more than 1000 total participants [25][26][27][28][29] ; four of the five trials are complete and one is ongoing. We report the current integrated RBL safety results from the largest safety database of any microbiota-based live biotherapeutic product.…”

Treating Clostridioides difficile: Could Microbiota-based Live Biotherapeutic Products Provide the Answer?

“…In the Phase 2B trial, recurrence rates were 18.8% for RBL compared to 51.8% for placebo. 25 In the Phase 3 trial, recurrence rates were 11.1% for RBL compared to 36.4% for placebo, with a P -value of 0.002. These results confirmed the efficacy of RBL in reducing the recurrence of CDI.…”

Prescription Microbiome Therapeutic for Recurrent Clostridioides difficile Infection: Fecal Microbiota Live-jslm

“…Patients with 2 or more recurrent CDI episodes or 2 episodes of severe CDI resulting in hospitalization were included. Immunocompromised patients or those with multifactorial diarrhea or nonresolving diarrhea with antibiotics were excluded (11,12). The primary end point of treatment success at 8 weeks of the randomized phase 2 dose-finding study was not met because treatment success was achieved by 55.6% of those who received 2 doses, 56.8% of those treated with 1 dose, and 43.2% of those who were administered 2 doses of placebo, suggesting no differences among the 3 groups (12).…”

“…Immunocompromised patients or those with multifactorial diarrhea or nonresolving diarrhea with antibiotics were excluded (11,12). The primary end point of treatment success at 8 weeks of the randomized phase 2 dose-finding study was not met because treatment success was achieved by 55.6% of those who received 2 doses, 56.8% of those treated with 1 dose, and 43.2% of those who were administered 2 doses of placebo, suggesting no differences among the 3 groups (12). An additional phase 2 open-label trial compared patients treated with 2 doses of RBL with historical controls showed treatment success at 8 weeks in 78.9% in the active arm compared with 30.7% in the historical control arm, with a durable treatment effect with 91% of evaluable primary responders remained CDI occurrence-free to 24 months (13).…”