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OP001 A phase III randomised controlled trial of Cx601, expanded allogeneic adipose-derived mesenchymal stem cells (eASC), for complex perianal fistulas in Crohns disease

J. Panés*1, D. García-Olmo2, G. Van Assche3, J. F. Colombel4, W. Reinisch5, D. C. Baumgart6, M. Nachury7, M. Ferrante3, L. Kazemi-Shirazi5, J. C. Grimaud8, F. de la Portilla9, E. Goldin10, A. Leselbaum11, M. C. Diez11, S. Danese12

1Hospital Clinic Barcelona, Barcelona, Spain, 2Hospital U. Fundación Jiménez-Díaz, Madrid, Spain, 3University Hospitals Leuven, KU Leuven, Leuven, Belgium, 4Icahn School of Medicine at Mount Sinai, New York, New York, United States, 5Medical University of Vienna, Vienna, Austria, 6Charité Medical School - Humboldt-University of Berlin, Berlin, Germany, 7CHU Lille, Lille, France, 8Hôpital Nord, Marseille, France, 9Hospital Virgen del Rocío, Sevilla, Spain, 10Sharee Zedek MC, Jerusalem, Israel, 11TiGenix, Madrid, Spain, 12Istituto Clinico Humanitas, Milano, Italy

Background

Complex perianal fistulas, a common complication of Crohn’s disease, are challenging to treat because many patients (pts) do not respond to current medical treatments. The objectives of this study were to assess the efficacy and safety of Cx601 added on to current treatment in pts refractory to antibiotics, immunosuppressants, and/or anti-tumour necrosis factor (TNF) therapy (NCT01541579).

Methods

This phase III, double-blind, parallel-group, multicentre study randomised pts (1:1 ratio) with non- or mildly active luminal Crohn’s disease (Crohn’s disease activity index (CDAI ≤ 220) and complex active perianal fistulas (high tract, active drainage during the prior 6 weeks [wk], ≤ 2 internal and ≤ 3 external openings assessed clinically, and with pelvic MRI) to Cx601 (single injection of 120 million eASC to all tracts) or placebo (PBO). Pts were allowed to continue current medical treatment without modification in the study period. Enrolled pts underwent fistula curettage and seton placement (if indicated) ≥ 2 wk before study treatment. The primary endpoint was combined remission at wk 24: clinical assessment of closure of all treated external openings that were draining at baseline, despite gentle finger compression, and absence of collections > 2 cm of the treated perianal fistulas confirmed by blinded MRI assessment. Key secondary endpoints were clinical remission (closure of all treated external openings) and response (closure of ≥ 50% of all treated external openings) by wk 24.

Results

Randomised were 212 pts (ITT set; mean age, 38.3 yr; male, 54.7%; Caucasian,92.5%): 107 to Cx601 and 105 to PBO. A significantly greater proportion of Cx601-treated pts in the ITT set achieved combined remission at wk 24 vs PBO: 49.5% vs 34.3%, p = 0.024; relative risk (RR) 95% confidence interval (CI): 1.42 (0.98–2.06). This result was confirmed in the modified ITT set (randomised and treated pts with ≥ 1 post-baseline efficacy assessment): Cx601 (n = 103) 51.5% vs PBO (n = 101) 35.6%, p = 0.021; RR (95% CI) 1.42 (0.99–2.04). In the modified ITT set, a numerically greater proportion of Cx601-treated pts achieved clinical remission (55.3% vs 42.6%, p = 0.057), and a significantly greater proportion had a response (68.9% vs 55.4%; p = 0.045). The distributions of time to clinical remission and time to response were significantly different between the 2 groups (p < 0.05). Median time to clinical remission (6.7 vs 14.6 wk) and time to response (6.3 vs 11.7 wk) were approximately 2-fold shorter with Cx601 vs PBO. Cx601 was well tolerated, with a lower proportion of pts experiencing treatment-related adverse events compared with those on PBO: 17.5% vs 29.4%.

Conclusion

Cx601 (eASC) appears to be an effective and safe therapy for complex perianal fistulas in pts with Crohn’s disease who failed conventional or biological treatments.