# A71 SUBGROUP ANALYSIS OF CANADIAN PARTICIPANTS IN PUNCH CD3-OLS: A PHASE 3 OPEN-LABEL CLINICALSTUDY TO EVALUATE THE SAFETY AND EFFICACY OF FECAL MICROBIOTA, LIVE-JSLM, IN ADULTS WITH RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION

## TL;DR

This study shows that a new microbiota-based treatment is safe and effective for preventing recurring C. difficile infection in Canadian adults.

## Contribution

The study provides the first evaluation of a microbiota-based therapy for C. difficile in Canadian participants.

## Key findings

- 75.2% of Canadian participants had treatment success at 8 weeks.
- 90.9% of those with treatment success had a sustained clinical response at 6 months.
- Most adverse events were mild-to-moderate gastrointestinal issues.

## Abstract

Fecal microbiota, live-jslm (RBL) is the first United States (US) Food and Drug Administration-approved, single-dose, microbiota-based live biotherapeutic product to prevent recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotics. In a prospective phase 3, open-label study (PUNCH CD3-OLS; NCT03931941) conducted in the US and Canada, RBL demonstrated a 73.8% treatment success rate at 8 weeks and a 91.0% sustained clinical response rate through 6 months.

To evaluate the safety and efficacy of RBL in Canadian participants in PUNCH CD3-OLS.

PUNCH CD3-OLS participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and immunocompromising conditions due to disease and/or medications were permitted to enroll. A single dose of RBL was rectally administered within 24–72h of SOC antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success at 8 weeks and sustained clinical response at 6 months after RBL administration.

Of the 697 participants who received RBL, 117 were Canadian. Participants in Canada were mostly White (91.5%) and female (70.1%) with a mean (SD) age of 61.3 years (17.38). Twenty participants (17.1%) were hospitalized for their qualifying episode. Participants’ medical histories included IBD (unspecified, [1.7%, n=2]; Crohn’s disease, [6.0%, n=7]; ulcerative colitis, [5.1%, n=6]), IBS (6.8%, n=8), and mild-to-moderate immunocompromising conditions (7.7 %, n=9). TEAEs through 8 weeks after RBL administration were reported by 59.8% of participants; most were gastrointestinal (48.7%, n=57) and mild-to-moderate in severity. Serious TEAEs were reported by 5.1% of participants within 8 weeks of RBL administration. At 8 weeks, 75.2% of participants (88/117) had treatment success; of those, 90.9% (80/88) had a sustained clinical response at 6 months. Demographics, safety, and efficacy outcomes were similar for participants in the US.

RBL was safe and efficacious for preventing rCDI among Canadian participants from PUNCH CD3-OLS, the largest study of a live microbiota-based therapy conducted to date.

NRCFerring Pharmaceuticals