Julián Panés1, Damián García-Olmo2, Gert Van Assche3, Jean Frederic Colombel4, Walter Reinisch5, Daniel C Baumgart6, Axel Dignass7, Maria Nachury8, Marc Ferrante3, Lili Kazemi-Shirazi9, Jean C Grimaud10, Fernando de la Portilla11, Eran Goldin12, Marie Paule Richard13, Mary Carmen Diez13, Ignacio Tagarro13, Anne Leselbaum14, Silvio Danese15. 1. Department of Gastroenterology, Hospital Clínic, IDIBAPS, CIBERehd, Barcelona, Spain. Electronic address: jpanes@clinic.cat. 2. Department of Surgery, Hospital U. Fundación Jiménez Díaz, Madrid, Spain. 3. Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. 4. Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York. 5. Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; McMaster University, Hamilton, Ontario, Canada. 6. Department of Gastroenterology and Hepatology, Charité Medical School - Humboldt-University of Berlin, Berlin, Germany. 7. Department of Medicine I, Agaplesion Markus Hospital, Frankfurt, Germany. 8. Department of Gastroenterology and Hepatology, CHU Lille, Lille, France. 9. Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria. 10. Department of Hepato-Gastroenterology, Hôpital Nord, Marseille, France. 11. Department of Surgery, Unit of Coloproctology, University Virgen del Rocio Hospital/IBiS/CSIC/University of Seville, Seville, Spain. 12. Digestive Diseases Institute, Sharee Zedek MC, Jerusalem, Israel. 13. TiGenix, Parque Tecnológico de Madrid, Madrid, Spain. 14. TiGenix, Parque Tecnológico de Madrid, Madrid, Spain; CDD-Clinical Drug Development, S.L., Barcelona, Spain. 15. Department of Gastroenterology, Istituto Clinico Humanitas IRCCS, Milano, Italy.
Abstract
BACKGROUND & AIMS: 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. METHODS: 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). 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 percentage points; 97.5% confidence interval [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 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; adverse events occurred in 76.7% of patients in the Cx601 group and 72.5% of patients in the control group. CONCLUSION: In a phase 3 trial of patients with Crohn's disease and 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.
RCT Entities:
BACKGROUND & AIMS: 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. METHODS: 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). 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 percentage points; 97.5% confidence interval [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 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; adverse events occurred in 76.7% of patients in the Cx601 group and 72.5% of patients in the control group. CONCLUSION: In a phase 3 trial of patients with Crohn's disease and 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.
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