Darvadstrocel in Patients With Crohn's Disease With Complex Perianal Fistulas: The ADMIRE CD II Phase 3 Randomized Trial.

BACKGROUND & AIMS: The ADMIRE CD trial demonstrated the efficacy and safety of darvadstrocel in patients with complex perianal fistulas from Europe and Israel. The efficacy and safety of darvadstrocel in an expanded patient population was investigated. METHODS: ADMIRE CD II (ClinicalTrials.gov, Number: NCT03279081) was a phase 3, double-blind, randomized, placebo-controlled trial conducted in Europe, Israel, and North America. Adults with Crohn's disease and complex perianal fistulas with ≤2 internal openings and ≤3 external openings and inadequate response to immunosuppressive agents or biologics were randomized 1:1 to receive darvadstrocel (a dispersion of 120 × 106 stem cells in 24 mL sterile buffered solution) or placebo. Both groups underwent curettage and closure of the internal opening. The primary endpoint was combined remission (closure of all treated external openings and absence of collections >2 cm) at week 24. RESULTS: Overall, 568 patients were randomized to receive darvadstrocel (n = 283) or placebo (n = 285); 249 and 246, respectively, completed the trial. At week 24, combined remission was achieved in 138 of 283 (48.8%) patients in the darvadstrocel group and 132 of 285 (46.3%) in the placebo group (estimated treatment difference: 2.4%; 95% CI, -5.8 to 10.6; P = .571). There were no significant differences in key secondary endpoints for darvadstrocel vs placebo (clinical remission at week 24 [P = .515] and time to clinical remission [P = .374]). Treatment-emergent adverse events were infrequent and experienced by similar proportions of patients receiving darvadstrocel (203/278 [73.0%]) and placebo (201/274 [73.4%]). CONCLUSIONS: ADMIRE CD II did not meet its primary endpoint of combined remission at week 24, with no statistically significant difference between darvadstrocel and placebo. No new safety signals were identified for darvadstrocel. CLINICALTRIALS: gov, Number: NCT002209456.