Safety and Efficacy of Adipose-Derived Stem Cells to Treat Complex Perianal Fistulas Patients With Crohn's Disease

NCT01378390 | Terminated Phase 3 DMC

• 2 other identifiers: CX-401/FATT2EudraCT: 2008-004286-25
• Study Type: interventional
• Target: 56
• Locations: 3 countries
• Sites: 12

Brief Summary

The purpose of this study is to determine safety and efficacy of eASCs (expanded adult stem cells) for treatment of complex perianal fistulas in patients with Crohn's disease.

Conditions

Complex Perianal Fistula; Crohn Disease

Keywords

Complex perianal fistula; Crohn disease; Adipose-derived stem cells; Liposuction

Outcome Measures

Primary Outcomes (1)

• Percentage of subjects in whom the external openings of the treated perianal fistula have closed

  24 weeks

Secondary Outcomes (9)

• Percentage of subjects in whom the external openings of the treated perianal fistula have closed

  12 weeks

• Changes over time in the Perianal Disease Activity Index

  4, 10, 12, 16, 22 and 24 weeks

• Changes over time in the Crohn's Disease Activity Index

  10 and 22 weeks

• Changes over time in the MRI Score of Severity (MSS)

  12 and 24 weeks

• Quality of life assessment using the SF-36 questionnaire

  12 and 24 weeks

Study Arms (2)

ASCs

EXPERIMENTAL

Intralesional dose of 20 million cells at baseline with a possible second administration of 40 million cells in case of incomplete fistula closure following week 12 assessment.

Drug: Expanded autologous adipose-derived adult stem cells (eASCs)

Placebo

SHAM COMPARATOR

Instillation of saline solution into the fistulous tract, following identical tract preparation process as for the investigational treatment group.

Drug: Placebo

Interventions

Expanded autologous adipose-derived adult stem cells (eASCs) DRUG

Administration will be preceded by localization and closure of the internal opening. Cell treatment injection will be performed following Major Ambulatory Surgery standards. Patients will receive an intralesional dose of 20 million cells at baseline. 50% of the cell suspension will be placed into the fistula walls of the internal opening, with the remaining 50% being injected across the wall tracts of the target fistula. Patients without healing (complete fistula closure) at week 12 will receive a second dose of 40 million cells, using the same treatment approach.

Also known as: Cx401 (company code), Ontaril®

ASCs

Placebo DRUG

Administration will be preceded by localization and closure of the internal opening following Major Ambulatory Surgery standards. Subjects will be receiving one treatment cycle with placebo consisting of intralesional instillation of 5 ml saline solution. Patients without healing (complete fistula closure) following week 12 assessment will continue to receive standard of care until the primary assessment of fistula closure at week 24. Patients with incomplete fistula closure at week 24 will be offered the possibility of participating in a separate open-label, single arm study using the ASCs derived from the liposuction procedure.

Also known as: Normale saline solution

Placebo

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Patients with Crohn's disease diagnosed at least 12 months earlier in accordance with accepted clinical, endoscopic, anatomopathological and/or radiologic criteria
• Presence of complex perianal fistula with 3 or fewer fistulous tracts assessed by MRI
• Patients with persistent and active complex perianal fistula and non-active luminal Crohn's disease defined by a CDAI ≤ 200. (Complex perianal fistula is defined as a fistula that meets one or more of the following criteria: High fistulas \[high inter-sphincteric, high trans-sphincteric, extra-sphincteric or supra-sphincteric\], presence of 3 or fewer external openings \[tracts\] associated with a complex perianal fistula, or pain/fluctuation
• Good general state of health according to the findings of the clinical history and the physical examination
• Women of a childbearing age with negative serum or urine pregnancy test (sensitive to 25 IU hCG). Both men and women should use appropriate birth control methods defined by the investigator

You may not qualify if:

• Presence of severe proctitis (prominent friability, spontaneous bleeding, multiple erosions, deep ulcers) or dominant active luminal disease requiring immediate therapy, assessed by rectosigmoidoscopy
• Patients with a CDAI ≥201
• Patients with an abscess unless a complete toilet of the area with drainage of the collections and the absence of abscess and other collections is confirmed prior to treatment start
• The presence of setons unless removed prior to the study procedure
• Presence of \>3 fistulous tracts and/or external openings
• Patients with rectal and/or anal stenosis evaluated by rectoscopy or EUA
• Patients who have received infliximab or any other anti-TNF agent in the 8 weeks before the cell treatment administration
• Patients who have received tacrolimus or cyclosporine in the 4 weeks before the cell treatment administration
• Patients with rectovaginal fistula, anal fistula(s), and/or non-perianal enterocutaneous fistula
• Patients with HIV, HBV, HCV or treponema infection, whether active or latent
• Patients with malignant tumor, except for basal cell or cutaneous squamous cell carcinoma, or patients with a prior history of malignant tumors, unless the neoplastic disease has been in remission for the previous 5 years
• Patients with cardiopulmonary disease which, in the opinion of the investigator, is unstable or sufficiently serious to exclude the patient from the study.
• Patients with congenital or acquired immunodeficiencies
• Patients allergic to local anesthetics or gadolinium (MRI contrast)
• MRI is unfeasible, (e.g. due to the presence of pacemakers, hip replacements or severe claustrophobia)

Sponsors & Collaborators

• Tigenix S.A.U.: lead

Study Sites (12)

University of Vienna

Vienna, Austria

Location

Academic Medical Center

Amsterdam, Netherlands

Location

Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital de Sagunto

Sagunto, Valencia, 46520, Spain

Location

Hospital Reina Sofia

Córdoba, 14004, Spain

Location

Complejo Hospitalario de León

Léon, 24071, Spain

Location

Hospital Universitario de la Princesa

Madrid, 28006, Spain

Location

Hospital Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Puerta de Hierro

Madrid, 28035, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Complejo Hospitalario de Pontevedra

Pontevedra, 36001, Spain

Location

Related Publications (4)

• Garcia-Olmo D, Garcia-Arranz M, Garcia LG, Cuellar ES, Blanco IF, Prianes LA, Montes JA, Pinto FL, Marcos DH, Garcia-Sancho L. Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn's disease: a new cell-based therapy. Int J Colorectal Dis. 2003 Sep;18(5):451-4. doi: 10.1007/s00384-003-0490-3. Epub 2003 May 20.

  PMID: 12756590 BACKGROUND

• Garcia-Olmo D, Garcia-Arranz M, Herreros D, Pascual I, Peiro C, Rodriguez-Montes JA. A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum. 2005 Jul;48(7):1416-23. doi: 10.1007/s10350-005-0052-6.

  PMID: 15933795 BACKGROUND

• Garcia-Olmo D, Herreros D, Pascual M, Pascual I, De-La-Quintana P, Trebol J, Garcia-Arranz M. Treatment of enterocutaneous fistula in Crohn's Disease with adipose-derived stem cells: a comparison of protocols with and without cell expansion. Int J Colorectal Dis. 2009 Jan;24(1):27-30. doi: 10.1007/s00384-008-0559-0. Epub 2008 Aug 12.

  PMID: 18696086 BACKGROUND

• Garcia-Olmo D, Garcia-Arranz M, Herreros D. Expanded adipose-derived stem cells for the treatment of complex perianal fistula including Crohn's disease. Expert Opin Biol Ther. 2008 Sep;8(9):1417-23. doi: 10.1517/14712598.8.9.1417.

  PMID: 18694359 BACKGROUND

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Damián García-Olmo, MD

  General Surgery Department, Hospital Universitario La Paz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2011
• First Posted: June 22, 2011
• Study Start: December 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: April 12, 2019

Record last verified: 2019-04

Locations

NL (1); AU (1); ES (10)