P0181 - Efficacy and Safety of Fecal Microbiota, Live-jslm in Older Participants With Recurrent Clostridioides difficile Infection and Underlying Comorbidities: An Ad Hoc Analysis of an Open-Label, Phase 3 Study
PACT Gastroenterology Center and Yale School of Medicine Hamden, Connecticut
Cirle A.. Warren, MD1, Glenn Tillotson, PhD2, Beth Guthmueller, 3, Joan Thul, BA4, Paul Feuerstadt, MD, FACG5, Anne J.. Gonzales-Luna, PharmD6, Travis J.. Carlson, PharmD7 1University of Virginia, Charlottesville, VA; 2GST Micro, North, VA; 3Rebiotix Inc., a Ferring Company, Roseville, MN; 4Ferring Pharmaceuticals, Inc., Parsippany, NJ; 5PACT Gastroenterology Center and Yale School of Medicine, Hamden, CT; 6University of Houston College of Pharmacy, Houston, TX; 7High Point University Fred Wilson School of Pharmacy, High Point, NC
Introduction: Advanced age and certain underlying comorbidities are among the risk factors for recurrent Clostridioides difficile infection (rCDI). PUNCH CD3-OLS (NCT03931941) is an ongoing, open-label, phase 3 trial designed to evaluate the efficacy and safety of fecal microbiota, live-jslm (RBL; REBYOTA™, previously known as RBX2660), the first microbiota-based live biotherapeutic product approved by the FDA to prevent rCDI in adults. Here, we report an ad hoc subgroup analysis of older participants with common comorbidities.
Methods: PUNCH CD3-OLS participants are ≥18 years old with documented rCDI as determined by the treating physician and confirmed using standard-of-care (SOC) methods, including NAAT or EIA assays. Within 24 h to 72 h after completing SOC antibiotics, participants received a single dose of RBL administered rectally. In this subgroup analysis, outcomes of participants ≥65 years old with at least one of the following underlying comorbidities were assessed: cardiac disorders, chronic kidney disease (CKD), and gastrointestinal (GI) disorders. The primary outcome was treatment success, defined as absence of CDI recurrence for 8 weeks after treatment. Participants were monitored for recurrence and treatment-emergent adverse events (TEAEs) up to 6 months after treatment.
Results: In the modified intent-to-treat population, 43% (172/402) of participants with adjudicated outcomes were ≥65 years old. Of these 172 participants, 50% had cardiac disorders (including atrial fibrillation and coronary artery disease), 16% had CKD, and 53% had GI disorders (including gastroesophageal reflux disease, irritable bowel syndrome, and ulcerative colitis); 27% of participants were in 2 of the comorbidity subgroups and 8% were in all 3. Across all subgroups, participants had an average of ≥3 prior CDI episodes and Charlson Comorbidity Index scores ≥5 at the time of enrollment. RBL treatment success rates were 63% for those with cardiac disorders, 63% for those with CKD, and 70% for those with GI disorders. In the safety population (N=483), the overall incidence of TEAEs in older participants with cardiac disorders, CKD, or GI disorders was 73%, 70%, and 65%, respectively; most TEAEs were mild or moderate in severity and deemed unrelated to treatment by the treating physician.
Discussion: RBL treatment remains effective in a cohort of older participants with multiply recurrent CDI and common comorbidities. The safety profile was consistent with that observed in previous clinical trials investigating RBL.
Disclosures:
Cirle Warren: Seres-109 of Seres Therapeutics and Aimmune – Advisory Committee/Board Member.
Anne Gonzales-Luna: Cidara Therapeutics – Grant/Research Support, Payment to institution. Ferring Pharmaceuticals – Independent Contractor, Personal fees. Innoviva Specialty Therapeutics – Independent Contractor, Personal fees. Paratek Pharmaceuticals – Grant/Research Support, grant payment made to institution. Seres Therapeutics – Grant/Research Support, grant payment made to institution.
Travis Carlson: American Society of Health-System Pharmacists (ASHP), which was funded via an educational grant from Ferring – Honorarium.
Cirle A.. Warren, MD1, Glenn Tillotson, PhD2, Beth Guthmueller, 3, Joan Thul, BA4, Paul Feuerstadt, MD, FACG5, Anne J.. Gonzales-Luna, PharmD6, Travis J.. Carlson, PharmD7. P0181 - Efficacy and Safety of Fecal Microbiota, Live-jslm in Older Participants With Recurrent Clostridioides difficile Infection and Underlying Comorbidities: An Ad Hoc Analysis of an Open-Label, Phase 3 Study, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.