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

This study has been terminated.
(After the investigators and experts in the field imput it became apparent that the protocol was not reflective of clinical reality. No safety issues reported.)
Sponsor:
Information provided by:
Cellerix
ClinicalTrials.gov Identifier:
NCT01378390
First received: June 21, 2011
Last updated: NA
Last verified: June 2011
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Complex Perianal Fistula
Crohn Disease
Drug: Expanded autologous adipose-derived adult stem cells (eASCs)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Single-blind, Placebo Controlled Multicenter Phase III Study to Assess the Efficacy and Safety of Expanded Autologous Adipose-derived Stem Cells (ASCs) (CX-401), for Treatment of Complex Perianal Fistulas in Perianal Crohn's Disease

Resource links provided by NLM:


Further study details as provided by Cellerix:

Primary Outcome Measures:
  • Percentage of subjects in whom the external openings of the treated perianal fistula have closed [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of subjects in whom the external openings of the treated perianal fistula have closed [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Changes over time in the Perianal Disease Activity Index [ Time Frame: 4, 10, 12, 16, 22 and 24 weeks ] [ Designated as safety issue: No ]
  • Changes over time in the Crohn's Disease Activity Index [ Time Frame: 10 and 22 weeks ] [ Designated as safety issue: No ]
  • Changes over time in the MRI Score of Severity (MSS) [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
  • Quality of life assessment using the SF-36 questionnaire [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
  • Percentage of subjects for whom surgery is avoided [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: 4, 10, 12, 16, 22 and 24 weeks ] [ Designated as safety issue: Yes ]
  • Clinically relevant variations in vital signs [ Time Frame: 4, 10, 12, 16, 22 and 24 weeks ] [ Designated as safety issue: Yes ]
  • Clinically relevant variations in laboratory tests [ Time Frame: 4, 10, 12, 16, 22 and 24 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 56
Study Start Date: December 2008
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ASCs
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)
Administration will be preceded by localization and closure of the internal opening. Cell treatment injection will be performed following Major Ambulatory Surgey standards. Patients will receive an intralesional dose of 20 million cells at baseline. 50% of the cell susupension 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.
Other Names:
  • Cx401 (company code)
  • Ontaril®
Sham Comparator: Placebo
Instillation of saline solution into the fistulous tract, following identical tract preparation process as for the investigational treatment group.
Drug: Placebo
Administration will be preceded by localization and closure of the internal opening following Major Ambulatory Surgey 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.
Other Name: Normale saline solution

Detailed Description:

Complex perianal fistulas are a source of great distress for suffers. In Crohn's disease, options are limited, and surgery is often associated with incontinence and recurrence.

The biological properties of stem cells derived from adult tissues make them candidates for the treatment of pathologies requiring tissue regeneration or in diseases where the healing process is altered.

A proof-of-concept study, a phase 1 study and a phase 2 study [Clinicaltrials.gov identifier: NCT00115466] have all suggested that this approach is promising, even in patients whose fistula is associated with Crohn's disease.

The present multicenter, placebo-controlled, phase 3 study aims to confirm the efficacy and safety shown in the previous phase 1 and phase 2 studies in the treatment of complex perianal fistulas in patients with Crohn's disease after 24 weeks from initial administration. Fistula closure is defined as absence of suppuration through the external orifice with complete re-epithelization of the external orifice and absence of collections >2cm directly related to the fistula tract treated, as measured by MRI.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 a history of abuse of alcohol or other addictive substances in the 6 months prior to inclusion
  • 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 any type of medical or psychiatric disease which, in the opinion of the investigator, could be grounds for exclusion from the study
  • Patients with congenital or acquired immunodeficiencies
  • Patients with abnormal laboratory test findings that contraindicate their inclusion in the study
  • 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)
  • Liposuction with extraction of at least 100 cm3 of fat from the abdominal wall is technically unfeasible or the patient does not consent to the procedure
  • Patients in need of surgery in the perianal region for reasons other than fistulas at the time of inclusion in the study, or a need for such surgery is foreseen in this region in the 26 weeks after treatment administration.
  • Patients who have suffered major surgery or severe trauma in the prior 6 months
  • Pregnant or breastfeeding women
  • Patients who do not wish to or cannot comply with study procedures
  • Patients currently receiving, or having received within 1 month prior to enrolment into this clinical trial, any investigational drug
  • Patients unlikely to comply with study procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01378390

Locations
Austria
University of Vienna
Vienna, Austria
Netherlands
Academic Medical Center
Amsterdam, Netherlands
Spain
Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Hospital de Sagunto
Sagunto, Valencia, Spain, 46520
Hospital Reina Sofia
Córdoba, Spain, 14004
Complejo Hospitalario de León
Léon, Spain, 24071
Hospital Gregorio Marañón
Madrid, Spain, 28007
Hospital Clínico San Carlos
Madrid, Spain, 28040
Hospital Ramón y Cajal
Madrid, Spain, 28034
Hospital Universitario de la Princesa
Madrid, Spain, 28006
Hospital Puerta de Hierro
Madrid, Spain, 28035
Complejo Hospitalario de Pontevedra
Pontevedra, Spain, 36001
Sponsors and Collaborators
Cellerix
Investigators
Principal Investigator: Damián García-Olmo, MD General Surgery Department, Hospital Universitario La Paz
  More Information

Publications:
Responsible Party: Guillermo Sellers, Vice Presient of Medical and Regulatory Affairs, Cellerix
ClinicalTrials.gov Identifier: NCT01378390     History of Changes
Other Study ID Numbers: CX-401/FATT2, EudraCT: 2008-004286-25
Study First Received: June 21, 2011
Last Updated: June 21, 2011
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Cellerix:
Complex perianal fistula
Crohn disease
Adipose-derived stem cells
Liposuction

Additional relevant MeSH terms:
Crohn Disease
Fistula
Rectal Fistula
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Pathological Conditions, Anatomical
Intestinal Fistula
Digestive System Fistula
Rectal Diseases

ClinicalTrials.gov processed this record on July 24, 2014