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

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Therapies for perianal fistulas in patients with Crohn's disease 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 Crohn's disease and perianal fistulas. We performed a double-blind study at 49 hospitals in Europe and Israel, comprising 212 patients with Crohn's disease 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, treated, 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). The study's primary endpoint, at week 24, was previously reported (combined remission in 51.5% of patients given Cx601 vs 35.6% ofcontrols, for a difference of 15.8 percentage points; 97.5% confidence interval[CI] 0.5-31.2; P= .021). At week 52, a significantly greaterproportion of patients given Cx601 achieved combined remission (56.3%) vs controls (38.6%) (adifference of 17.7 percentage points; 95% CI 4.2-31.2; P=.010), and clinical remission (59.2%vs 41.6% of controls, for a difference of 17.6 percentage points; 95% CI 4.1-31.1; P=.013). Safety was maintained throughout week 52; adverseevents occurred in 76.7% of patients in the Cx601group and 72.5% of patients in the control group. In aphase 3 trial of patients with Crohn's disease and treatment-refractory complex perianal fistulas, we found Cx601 to be safeand effective in closing external openings, compared withplacebo, after 1 year. ClinicalTrials.gov no:NCT01541579.