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OP009 Long-term efficacy and safety of Cx601, allogeneic expanded adipose-derived mesenchymal stem cells, for complex perianal fistulas in Crohn's disease: 52-week results of a phase III randomised controlled trial

Panes J.*1, García-Olmo D.2, Van Assche G.3, Colombel J.-F.4, Reinisch W.5, Baumgart D.C.6, Nachury M.7, Ferrante M.3, Kazemi-Shirazi L.5, Grimaud J.C.8, de la Portilla F.9, Goldin E.10, Richard M.P.11, Diez M.C.11, Danese S.12

1Hospital Clínic de Barcelona, Dept of Gastroenterology, Barcelona, Spain 2Hospital U. Fundaciόn Jiménez-Díaz, Madrid, Spain 3University Hospitals Leuven, KU Leuven, Leuven, Belgium 4Icahn School of Medicine at Mount Sinai, 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

Existing therapies for perianal fistulas in Crohn's disease (CD) are associated with a high failure rate and few have been evaluated in randomised controlled trials (RCTs) using hard endpoints. The 24-week results of a RCT showed that Cx601 added onto standard of care was safe and effective for treatment-refractory complex perianal fistulas with a significantly greater proportion of patients achieving clinical and radiological combined remission (CR) compared with placebo+standard of care. We aimed to determine whether this efficacy and safety was maintained over the long-term (52 weeks) (NCT01541579).

Methods

Patients with inactive or mildly active luminal CD and treatment-refractory, draining, complex perianal fistulas were randomised (1:1) to Cx601 (single injection of 120 million eASC to all tracts+standard of care) or control (placebo+standard of care) in this phase III, double-blind, parallel-group multicentre study. An unblinded surgeon administered the treatment and a blinded gastroenterologist evaluated the therapeutic effect. Efficacy was evaluated in the mITT (randomised, treated and ≥1 post-baseline efficacy assessment) population at week 52. Pre-specified endpoints included CR (closure of all treated external openings [EOs] that were draining at baseline assessed clinically, and absence of collections >2 cm in the area of the treated perianal fistulas by blinded central MRI reading) and clinical remission (closure of all treated EOs). Sustained CR at week 52 was also evaluated.

Results

212 patients were randomised to Cx601 (n=107) or control (n=105); 61.8% completed the 52-week follow-up (Cx601, n=70; control=61). The beneficial effect observed at week 24 (CR in Cx601 51.5%, control 35.6%; p=0.021) was sustained at week 52; a significantly greater proportion of patients receiving Cx601 vs control achieved CR (56.3% vs 38.6%; p=0.010), and clinical remission (59.2% vs 41.6%; p=0.013) at week 52. Of patients with CR at week 24, a greater proportion of those treated with Cx601 vs control had no relapse at week 52 (75.0% vs 55.9%). Rates and types of treatment related adverse events were similar in both groups (20.4%, Cx601 vs 26.5%, control).

Conclusion

The efficacy of Cx601 in treatment-refractory complex perianal fistulas of CD patients was sustained for up to 1 year after a single administration. The results also support the favourable tolerability of Cx601 over the long-term.