World Congress at ACG2017
Simultaneous Plenary Session 4C: IBD
82 - One-year Efficacy and Safety of a Single Dose of Cx601, Allogeneic Expanded Adipose-Derived Mesenchymal Stem Cells, for Complex Perianal Fistulas in Crohn’s Disease: Long-Term Results of a Phase 3, Randomized, Double-Blind Clinical Trial
Wednesday, October 18
10:00 AM - 10:10 AM
Location: W414 (Level 4)
Category: Practice Management
Daniel C. Baumgart, MD, PhD1, Julián Panés, MD2, Damián García-Olmo, MD3, Gert Van Assche, MD, PhD4, Jean F. Colombel, MD5, Walter Reinisch, MD6, Maria Nachury, MD7, Marc Ferrante, MD, PhD4, Lili Kazemi-Shirazi, MD6, Jean C. Grimaud, MD8, Fernando de la Portilla, MD9, Eran Goldin, MD10, Marie Paule Richard, MD11, Ignacio Tagarro, PhD11, Silvio Danese, MD, PhD12
1Charité Medical School - Humboldt-University of Berlin, Berlin, Germany; 2Hospital Clínic Barcelona, Barcelona, Spain; 3Hospital U. Fundación Jiménez-Díaz, Madrid, Spain; 4University Hospitals Leuven, KU Leuven, Leuven, Belgium; 5Icahn School of Medicine at Mount Sinai, New York, New York, USA; 6Medical University of Vienna, Vienna, Austria; 7Centre Hospitalier Régional Universitaire (CHRU) de Lille, Lille, France; 8Hôpital Nord, Marseilles, France; 9Hospital Virgen del Rocío, Seville, Spain; 10Sharee Zedek Medical Center, Jerusalem, Israel; 11TiGenix, Madrid, Spain; 12Istituto Clinico Humanitas, Milan, Italy
Introduction: Current therapies for complex perianal fistulas in Crohn’s disease (CD) are often ineffective. We aimed to assess the long-term efficacy and safety of Cx601, added on to current therapies, in CD patients with complex refractory perianal fistulas.
Methods: Patients with draining treatment-refractory complex perianal fistulas and inactive/mildly-active luminal CD (CDAI ≤220) were randomized to Cx601 arm (a single intralesional injection of 120 million eASC + standard of care), or to control arm (a single intralesional injection of placebo + standard of care) in a Phase 3, double-blind, parallel group, multicenter study. Before study treatment administration, patients underwent fistula curettage and, if indicated, seton placement and subsequent removal. Baseline concomitant medications, (immunosuppressants and/or anti-TNFs) were continued without dose or regimen modification; antibiotics were allowed for up to 4 weeks. One-year efficacy was evaluated in the mITT population (randomized, treated, and ≥1 post-baseline efficacy assessment). The main efficacy endpoint was combined remission (CR), a stringent parameter consisting of closure of all treated external openings, draining at baseline, and absence of collections >2 cm confirmed by blinded central MRI reading. LOCF rules were applied.
Results: Patients were randomized to Cx601 (n=103) or control (n=101); 61.8% of all randomized patients completed the one-year follow-up. CR at one year was achieved in 56.3% of patients in Cx601 group vs. in 38.6% of patients in control group (p=0.010). Sensitivity analyses on CR at one year based on alternative imputations of missing data were performed (Table).
Discussion: One year after the administration of study treatment, CR was observed in a significantly greater proportion of patients in the Cx601 group vs. control group, as it was observed at week 24 (reported earlier). Sensitivity analyses supported the advantage of Cx601 vs. control treatment for the long-term treatment of complex perianal fistulas in CD patients, providing evidence on the robustness of this advantage. Safety results up to one year post-administration confirmed that Cx601 does not appear to add any safety burden to standard of care treatments.
Disclosures: Does Disclose
Daniel C. Baumgart: Grants, Consulting Fees and Non-financial Support - AbbVie, Biogen, BMS, Dr. Falk, Ferring, Genentech-Roche, Janssen, MSD, Pfizer, Recordati, Shire, Takeda; Consulting Fees and Non-financial Support - Foreward Pharma, TiGenix; Grants – Celgene, Hitachi, Nestle, Shield Therapeutics.
Julian Panes: Consulting Fees – AbbVie, Boehringer-Ingelheim, Celgene, Galapagos, GSK, Janssen, MSD, Novartis, Pfizer, Oppilan, Takeda, TiGenix, Vivelix.
Damian Garcia-Olmos: Consulting Fees – TiGenix; Patent (10157355957US) and a Patent Pending (US11/167061).
Gert Van Assche: Consulting Fees - TiGenix; Grants, Consulting Fees - AbbVie, Ferring, Genentech-Roche, Janssen, MSD, Pfizer, Takeda.
Jean F. Colombel: Grants - AbbVie, Janssen, Takeda; Other Fees – Amgen, Boehringer-Ingelheim, Celgene Corporation, Celtrion, Enterome, Ferring, Genentech, Genefit, Intestinal Biotech Development, Medimmune, Merck & Co., Pfizer, Protagonist, Second Genome, Seres, Shire, Theradiag.
Walter Reinisch: Consulting Fees as a Speaker - Abbott Laboratories, AbbVie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor, Yakult; Consulting Fees as a Consultant - Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma, Astellas, AstraZeneca, Avaxia, Roland Berger GmBH, Bioclinica, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, Elan, Ernest & Young, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grunenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakka Kirin Pharma, Lipid Therapeutics, Mallinckrodt, MedImmune, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, Parexel, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Sigmoid, Takeda, Therakos, TiGenix, UCB, Vifor, Zealand, Zyngenia, and 4SC; Consulting Fees as an Advisor - Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma, Astellas, AstraZeneca, Avaxia, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, Elan, Ferring, Galapagos, Genentech, Grunenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakka Kirin Pharma, Lipid Therapeutics, MedImmune, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, TiGenix, UCB, Zealand, Zyngenia, and 4SC; Grants - Abbott Laboratories, AbbVie, Aesca, Centocor, Falk Pharma GmbH, Immundiagnostik, MSD.
Maria Nachury: Consulting Fees - Boehringer-Ingelheim, TiGenix; Consulting Fees and Non-financial Support: AbbVie, MSD, Takeda.
Marc Ferrante: Non-financial Support: TiGenix; Grants, Consulting Fees, Non-financial Support - Takeda; Consulting Fees and Non-financial Support – AbbVie, Boehringer-Ingelheim, Chiesi, Falk, Ferring, Janssen, MSD, Mitsubishi, Tillotts, Zeria.
Lili Kazemi-Sharazi: Non-financial and Other Support - TiGenix; Other Support: Sanofi, SigmaTau; Consulting Fees – Abbott, AbbVie, CSL-Behring, Chiesi, Ferring, MSD, MerckSerono/Dr. Falk, Novartis, Phadia Austria/Thermo Fisher Scientific Roche; Non-financial Support – Abbott, Gilead, MSD, MerckSerono/Dr. Falk, Mylan, Novartis.
Marie Paule Richard: Consulting Fees - TiGenix (employee).
Ignacio Tagarro: Consulting Fees - TiGenix (employee).
Silvio Danese: Consulting Fees - AbbVie, Allergan, Boehringer-Ingelheim, Celltrion, Ferring, Hospira, Janssen, MSD, Merck, Mundipharma, Pfizer, Sandoz, Takeda, UCB, Vifor.
All other authors have indicated no relevant financial relationships.
Citation: . ONE-YEAR EFFICACY AND SAFETY OF A SINGLE DOSE OF CX601, ALLOGENEIC EXPANDED ADIPOSE-DERIVED MESENCHYMAL STEM CELLS, FOR COMPLEX PERIANAL FISTULAS IN CROHN’S DISEASE: LONG-TERM RESULTS OF A PHASE 3, RANDOMIZED, DOUBLE-BLIND CLINICAL TRIAL. Program No. 82. World Congress of Gastroenterology at ACG2017 Meeting Abstracts. Orlando, FL: American College of Gastroenterology.