Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn’s Disease

Abstract Background & Aims Therapies for perianal fistulas in patients with Crohn's disease (CD) are often ineffective in producing long-term healing. We performed a randomized placebo-controlled trial to determine the long-term efficacy and safety of a single local administration of allogeneic expanded adipose-derived stem cells (Cx601) in patients with CD and perianal fistulas. Methods We performed a double-blind study at 49 hospitals in Europe and Israel, comprising 212 patients with CD and treatment-refractory, draining, complex perianal fistulas. Patients were randomly assigned (1:1) to groups given a single local injection of 120 million Cx601 cells or placebo (control), in addition to the standard of care. Efficacy endpoints evaluated in the modified intention to treat population (randomly assigned, given a test article, and with 1 or more post-baseline efficacy assessment) at week 52 included combined remission (closure of all treated external openings draining at baseline with absence of collections >2 cm, confirmed by magnetic resonance imaging) and clinical remission (absence of draining fistulas). Results The study's primary endpoint, at week 24, was previously reported (combined remission in 51.5% of patients given Cx601 vs 35.6% of controls, for a difference of 15.8%; 97.5% CI; 0.5%–31.2%; P=.021). At week 52, a significantly greater proportion of patients given Cx601 achieved combined remission (56.3%) vs controls (38.6%) (a difference of 17.7%; 95% CI, 4.2%–31.2%; P=.010), and clinical remission (59.2% vs 41.6% of controls, for a difference of 17.6%; 95% CI, 4.1%–31.1%; P=.013). Safety was maintained throughout week 52; adverse events occurred in 76.7% of patients in the Cx601 group and 72.5% patients in the control group. Conclusion In a phase 3 trial of patients with CD and treatment-refractory, treatment-refractory complex perianal fistulas, we found Cx601 to be safe and effective in closing external openings, compared with placebo, after 1 year. ClinicalTrials.gov no: NCT01541579.