Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn's Disease

NCT01541579 | Completed Phase 3

• 1 other identifier: Cx601-0302
• Study Type: interventional
• Target: 278
• Locations: 8 countries
• Sites: 52

Brief Summary

The current multicentre phase III study is proposed to confirm in an add-on therapy design compared to a placebo-control group, the efficacy of adipose-derived stem cells (eASCs) from healthy donors for the treatment of complex anal fistulas in patients with Crohn's disease over a 24-week period and an extended follow-up period up to 104 weeks.

Conditions

Crohn's Disease

Keywords

Perianal fistulising Crohn's disease.

Outcome Measures

Primary Outcomes (1)

• Combine remission of perianal fistulising Crohn's

  Combined Remission of perianal fistulising Crohn's disease defined as the clinical assessment of closure of all treated external openings (EO) that were draining at baseline despite gentle finger compression at week 24, and absence of collections \> 2 cm of the treated perianal fistulas confirmed by centrally blinded MRI assessment by week 24.

  24 weeks

Secondary Outcomes (4)

• Efficacy Assessment by week 24

  24 weeks

• Efficacy Assessment by week 52

  52 weeks

• Efficacy Assessment by week 104

  104 Weeks

• Safety analysis throughout the study:

  week 24, 52 and 104

Study Arms (2)

Treatment Arm

EXPERIMENTAL

Cx601 is a cell suspension in aseptic buffered solution containing human expanded adipose-derived stem cells (eASCs) of allogeneic origin in disposable vials with no preservative agents. The cells will be given at a dose of 120 million cells (5 million cells / mL) for intralesional injection.

Other: Cx601

Placebo-control group

PLACEBO COMPARATOR

Placebo (saline solution) will be given also for intralesional injection at the same quantity (volume, 24 mL) and following the same schedule.

Other: Saline solution

Interventions

Cx601 OTHER

120 million cells administered by intralesional injection.

Treatment Arm

Saline solution OTHER

24 mL saline solution by intralesional injection

Placebo-control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The reference population will consist of patients with perianal fistulising Crohn´s disease refractory to at least one of the following treatments: antibiotics, immunosuppressants or anti-tumor necrosis factor (TNF). Naïve patients are excluded, and those patients refractory to antibiotics will represent less than 25% of the total recruited patients.
• Signed informed consent.
• Patients with Crohn's Disease (CD) diagnosed at least 6 months earlier in accordance with accepted clinical, endoscopic, histological and/or radiologic criteria.
• High inter-sphincteric, trans-sphincteric, extra-sphincteric or supra-sphincteric.
• Presence of ≥ 2 external openings (tracts).
• Associated collections
• Non-active or mildly active luminal CD defined by a CDAI ≤ 220.
• Patients of either sex aged 18 years or older
• Good general state of health according to clinical history and a physical examination.
• For women of a childbearing age, they must have negative serum or urine pregnancy test (sensitive to 25 IU human chorionic gonadotropin (hCG)). Both men and women should use appropriate birth control methods defined by the investigator.

You may not qualify if:

• Presence of dominant luminal active Crohn's disease requiring immediate therapy.
• CDAI \>220.
• Concomitant rectovaginal fistulas
• Patient naïve to specific treatment for perianal fistulising Crohn's disease including antibiotics
• Presence of an abscess or collections \> 2 cm, unless resolved in the preparation procedure (week -3 to day 0).
• Presence of \> 2 fistular lesions.
• Presence of \> 3 external openings.
• Rectal and/or anal stenosis and / or active proctitis, if this means a limitation for any surgical procedure.
• Patient who underwent surgery for the fistula other than drainage or seton placement.
• Patient with diverting stomas
• Patient with ongoing steroid treatment or treated with steroids in the last 4 weeks
• Renal impairment defined by creatinine clearance below 60 ml/min calculated using Cockcroft-Gault formula or by serum creatinine ≥ 1.5 x upper limit of normality (ULN)
• Hepatic impairment defined by both of the following laboratory ranges:
• Total bilirubin ≥ 1.5 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase(ALT) ≥ 2.5 x ULN

Sponsors & Collaborators

• Tigenix S.A.U.: lead

Study Sites (52)

Univ.-Klinik Innsbruck

Innsbruck, 6020, Austria

Location

Krankenhaus

Saint Veit/Glan, 9300, Austria

Location

Medizinische Universität

Vienna, 1090, Austria

Location

Hospital Oost-Limburg

Genk, 3600, Belgium

Location

Gent University Hospital

Ghent, 9000, Belgium

Location

Leuven University Hospital

Leuven, 3000, Belgium

Location

Hospital Hartziekenhuis

Roeselare, 8800, Belgium

Location

CHU d'Amiens

Amiens, 80054, France

Location

CHU de Bordeaux

Bordeaux, 3300, France

Location

CHU de Caen

Caen, 14033, France

Location

Hôpital Beaujon

Clichy, France

Location

CHRU de Lille

Lille, 59037, France

Location

CHU de Marseille

Marseille, 13915, France

Location

CHU de Nice

Nice, 06202, France

Location

Hôpital Saint-Louis

Paris, France

Location

Charite

Berlin, 13353, Germany

Location

Krakenhaus Walfriede

Berlin, 14163, Germany

Location

Klinikum Braunscheweig

Braunschweig, 38126, Germany

Location

Evangelisches Krankenhaus Kalk

Cologne, 51103, Germany

Location

Klinikum Frankfurt

Frankfurt am Main, 60431, Germany

Location

Klinikum Lüneburg

Lüneburg, 21339, Germany

Location

Rambam MC

Haifa, 31096, Israel

Location

Sharee Zedek MC

Jerusalem, 91031, Israel

Location

Rabin MC

Petah Tikva, 49100, Israel

Location

Tel Aviv Sourasky MC

Tel Aviv, 64239, Israel

Location

Sheba MC

Tel Litwinsky, 52621, Israel

Location

Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant'Orsola Malpighi

Bologna, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

Location

Instituto Clinico Humanitas IRCCS

Milan, 20089, Italy

Location

Seconda Università degli Studi di Napoli

Napoli, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Azienda Ospedaliera San Camillo-Forlanini

Rome, 00149, Italy

Location

Università Cattolica del Sacro Cuore

Rome, 00168, Italy

Location

AMC

Amsterdam, Netherlands

Location

VUMC

Amsterdam, Netherlands

Location

Catharina Ziekenhuis

Eindhoven, 5623, Netherlands

Location

UMCU

Utrecht, Netherlands

Location

Hospital de Manises

Manises, Valencia, 46940, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Spain

Location

Hospital Juan Ramon Jimenez

Huelva, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Hospital Clinico San Carlos

Madrid, Spain

Location

Hospital La Princesa

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Son Espases

Palma de Mallorca, 07010, Spain

Location

Hospital de Montecelo

Pontevedra, Spain

Location

Hospital Virgen del Rocio

Seville, Spain

Location

Hospital de Sagunto

Valencia, Spain

Location

Hospital Universitario La Fe

Valencia, Spain

Location

Related Publications (3)

• Garcia-Olmo D, Gilaberte I, Binek M, D Hoore AJL, Lindner D, Selvaggi F, Spinelli A, Panes J. Follow-up Study to Evaluate the Long-term Safety and Efficacy of Darvadstrocel (Mesenchymal Stem Cell Treatment) in Patients With Perianal Fistulizing Crohn's Disease: ADMIRE-CD Phase 3 Randomized Controlled Trial. Dis Colon Rectum. 2022 May 1;65(5):713-720. doi: 10.1097/DCR.0000000000002325.

  PMID: 34890373 DERIVED

• Panes J, Garcia-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Diez MC, Tagarro I, Leselbaum A, Danese S; ADMIRE CD Study Group Collaborators. Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease. Gastroenterology. 2018 Apr;154(5):1334-1342.e4. doi: 10.1053/j.gastro.2017.12.020. Epub 2017 Dec 24.

  PMID: 29277560 DERIVED

• Panes J, Garcia-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Leselbaum A, Danese S; ADMIRE CD Study Group Collaborators. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial. Lancet. 2016 Sep 24;388(10051):1281-90. doi: 10.1016/S0140-6736(16)31203-X. Epub 2016 Jul 29.

  PMID: 27477896 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Julian Panes, MD

  Hospital Clinic of Barcelona

  STUDY CHAIR

• Julian Panes, MD

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

• Lili Kazemi-Shirazi, Professor

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

• Karl Mrak, MD

  Krankenhaus, St. Veit/Glan

  PRINCIPAL INVESTIGATOR

• Marc Ferrante, MD

  Universitaire Ziekenhuizen KU Leuven

  PRINCIPAL INVESTIGATOR

• Kurt Van der Speeten, MD

  Hospital Oost-Limburg, Genk

  PRINCIPAL INVESTIGATOR

• Danny de Looze, Professor

  Gent University Hospital

  PRINCIPAL INVESTIGATOR

• Filip Baert, MD

  Hospital Hartziekenhuis, Roeselare

  PRINCIPAL INVESTIGATOR

• Daniel C Baumgart, Professor

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

• Axel Dignass, Professor

  Kilikum Frankfurt

  PRINCIPAL INVESTIGATOR

• Max Reinshagen, Professor

  Kinikum Braunschweig

  PRINCIPAL INVESTIGATOR

• Silvio Danese, MD

  Instituto Clinico Humanitas IRCCS, Milano

  PRINCIPAL INVESTIGATOR

• Vito Annese, MD

  Azienda Ospedaliero-Universitaria Careggi

  PRINCIPAL INVESTIGATOR

• Anna Kohn, MD

  Azienda Ospedaliera San Camillo-Forlanini, Rome

  PRINCIPAL INVESTIGATOR

• Alfredo Papa, MD

  Università Cattolica del Sacro Cuore, Rome

  PRINCIPAL INVESTIGATOR

• Giacomo C Sturniolo, Professor

  Azienda Ospedaliera di Padova

  PRINCIPAL INVESTIGATOR

• Andrea Belluzi, MD

  Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant'Orsola Malpighi

  PRINCIPAL INVESTIGATOR

• Gabriele Riegler, Professor

  University of Campania Luigi Vanvitelli

  PRINCIPAL INVESTIGATOR

• Bas Oldenburg, MD

  UMCU, Utrecht

  PRINCIPAL INVESTIGATOR

• Adriaan A van Bodegraven, MD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

• Gigs van den Brink, Professor

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

• María D Martín Arranz, MD

  Hospital Universitario La Paz

  PRINCIPAL INVESTIGATOR

• Jose M Gallardo Valverde, MD

  Hospital Universitario Reina Sofía, Cordoba

  PRINCIPAL INVESTIGATOR

• Javier Pérez Gisbert, MD

  Hospital La Princesa, Madrid

  PRINCIPAL INVESTIGATOR

• Belén Beltrán Niclós, MD

  Hospital Universitario La Fe

  PRINCIPAL INVESTIGATOR

• Carlos Taxonera Samsó, MD

  Hospital Clínico San Carlos, Madrid

  PRINCIPAL INVESTIGATOR

• Fernando de la Portilla de Juan, MD

  Hospital Virgen del Rocío, Seville

  PRINCIPAL INVESTIGATOR

• Ricardo Rada Morgades, MD

  Hospital Juan Ramón Jiménez, Huelva

  PRINCIPAL INVESTIGATOR

• Gonzalo Gómez Gómez, MD

  Hospital Universitario 12 de Octubre, Madrid

  PRINCIPAL INVESTIGATOR

• Daniel Carpio López, MD

  Hospital de Montecelo, Pontevedra

  PRINCIPAL INVESTIGATOR

• Xavier Cortés Rizo, MD

  Hospital de Sagunto, Valencia

  PRINCIPAL INVESTIGATOR

• Torsten Kucharzik, Professor

  Klinikum Lüneburg

  PRINCIPAL INVESTIGATOR

• Andreas Sturm, Professor

  Krakenhaus Walfriede, Berlin

  PRINCIPAL INVESTIGATOR

• Antonio López Sanromán, MD

  Hospital Universitario Ramon y Cajal

  PRINCIPAL INVESTIGATOR

• Joaquín Hinojosa de Val, MD

  Hospital de Manises, Valencia

  PRINCIPAL INVESTIGATOR

• Xavier González Argenté, MD

  Son Espases, Palma de Mallorca

  PRINCIPAL INVESTIGATOR

• Maria Nachury, MD

  CHRU de Lille

  PRINCIPAL INVESTIGATOR

• Frank Zerbib, MD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Stéphanie Viennot, MD

  University Hospital, Caen

  PRINCIPAL INVESTIGATOR

• Jean-Louis Dupas, MD

  Centre Hospitalier Universitaire, Amiens

  PRINCIPAL INVESTIGATOR

• Jean-Charles Grimaud, MD

  CHU de Marseille

  PRINCIPAL INVESTIGATOR

• Xavier Hebuterne, Professor

  Centre Hospitalier Universitaire de Nice

  PRINCIPAL INVESTIGATOR

• Matthieu Allez, Professor

  Hôpital Saint Louis Paris

  PRINCIPAL INVESTIGATOR

• Yoram Bouhnik, MD

  Hôpital Beaujon, Clichy

  PRINCIPAL INVESTIGATOR

• Matti Waterman, MD

  Rambam MC, Haifa

  PRINCIPAL INVESTIGATOR

• Shomron Ben-Horin, MD

  Sheba MC, Tel Hashomer

  PRINCIPAL INVESTIGATOR

• Sigal Fishman, MD

  Tel Aviv Sourasky MC, Tel Aviv

  PRINCIPAL INVESTIGATOR

• Eran Goldin, Professor

  Sharee Zedek MC, Jerusalem

  PRINCIPAL INVESTIGATOR

• Irit Avni-Biron, MD

  Rabin MC, Petah Tikva

  PRINCIPAL INVESTIGATOR

• Herbert Tilg, Professor

  Univ.-Klinik Innsbruck

  PRINCIPAL INVESTIGATOR

• Lennard Gilissen, MD

  Catharina Ziekenhuis Eindhoven

  PRINCIPAL INVESTIGATOR

• Carlos Pastor, MD

  Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz

  PRINCIPAL INVESTIGATOR

• Wolfgang Kruis, Professor

  Evangelisches Krankenhaus Kalk, Köln

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2012
• First Posted: March 1, 2012
• Study Start: July 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: November 1, 2016
• Last Updated: November 29, 2019

Record last verified: 2019-11

Locations

IL (5); DE (6); FR (8); AU (3); IT (7); NL (4); BE (4); ES (15)