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Autologous Expanded Adipose-Derived Stem Cells for the Treatment of Complex Cryptoglandular Perianal Fistulas: A Phase III Randomized Clinical Trial (FATT 1 Fistula Advanced Therapy Trial 1) and Long-term Evaluation

Herreros, M.D. M.D., Ph.D.; Garcia-Arranz, M. Ph.D.; Guadalajara, H. M.D.; De-La-Quintana, P. Ph.D.; Garcia-Olmo, D. M.D., Ph.D.and the FATT Collaborative Group

Diseases of the Colon & Rectum: July 2012 - Volume 55 - Issue 7 - p 762–772
doi: 10.1097/DCR.0b013e318255364a
Original Contribution

Background: Autologous adipose-derived stem cells may represent a novel approach for the management of complex fistula-in-ano. After successful phase I and II clinical trials, a phase III trial was performed to investigate the safety and efficacy.

Design: In this multicenter, randomized, single-blind, add-on clinical trial, 200 adult patients from 19 centers were randomly assigned to receive 20 million stem cells (group A, 64 patients), 20 million adipose-derived stem cells plus fibrin glue (group B, 60 patients), or fibrin glue (group C, 59 patients) after closure of the internal opening. Fistula healing was defined as reepithelization of the external opening and absence of collection >2 cm by MRI. If the fistula had not healed at 12 weeks, a second dose (40 million stem cells in groups A and B) was administered. Patients were evaluated at 24 to 26 weeks (primary end point) and at 1 year (long-term follow-up).

Results: All results are according to the “blinded evaluator” assessment. After 24 to 26 weeks, the healing rate was 39.1%, 43.3%, 37.3% in groups A, B, and C (p = 0.79). At 1 year, the healing rates were 57.1%, 52.4%, and 37.3 % (p = 0.13). On analysis of the subpopulation treated at the technique’s pioneer center, healing rates were 54.55%, 83.33%, and 18.18%, at 24 to 26 weeks (p < 0.001). No SAEs were reported.

Conclusions: In treatment of complex fistula-in-ano, a dose of 20 or 60 million adipose-derived stem cells alone or in combination with fibrin glue was considered a safe treatment, achieving healing rates of approximately 40% at 6 months and of more than 50% at 1-year follow-up. It was equivalent to fibrin glue alone. No statistically significant differences were found when the 3 groups where compared. Clinical trials registration: www.clinicaltrials.gov, identifier NCT00475410; Sponsor, Cellerix SA.

Department of Surgery and Cell Therapy, La Paz University Hospital, Universidad Autonoma de Madrid, Hospital La Paz IdiPaz, Madrid, Spain

Financial Disclosures: Prof D. García-Olmo is Chairman of the UAM-Cellerix Cell Therapy and Regenerative Medicine Department, to which Cellerix has contributed €40,000 per year. UAM and Cellerix S.A. share patent rights to Cx401 (Adipose Derived Stem Cells). Prof D. García-Olmo is a member of the Advisory Board of Cellerix. M. Garcia-Arranz and Prof D. García-Olmo have applied for 2 patents related to Cx401 titled “Identification and isolation of multipotent cells from non-osteochondral mesenchymal tissue” (WO 2006/057649) and “Use of adipose tissue-derived stromal stem cells in treating fistula” (WO 2006/136244).

Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Vancouver, BC, Canada, May 14 to 18, 2011.

Clinical trial registration at www.clinicaltrials.gov: ID NCT00475410, Efficacy and Safety of Adipose Stem Cells to Treat Complex Perianal Fistulas Not Associated to Crohn’s Disease (FATT1); and ID NCT01020825, Long-term Safety and Efficacy of Adipose-Derived Stem Cells to Treat Complex Perianal Fistulas in Patients Participating in the FATT-1 Randomized Controlled Trial (LTE).

The European Medicines Agency (EMA) granted Cx401 (Autologous Expanded Adipose-Derived Stem Cells (eASCs)) “Orphan Drug” status in 2005 for the treatment of anal fistula (Orphan Designation EU number EU/3/05/303).

Correspondence: Maria Dolores Herreros, M.D., PhD., Colorectal Surgery Unit, Department of General Surgery, La Paz University Hospital, Paseo de La Castellana 261, 28046 Madrid, Spain. E-mail: loles.herreros@gmail.com

© 2012 The American Society of Colon and Rectal Surgeons