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

Primary Purpose

Complex Perianal Fistula, Crohn Disease

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Expanded autologous adipose-derived adult stem cells (eASCs)
Placebo
Sponsored by
Tigenix S.A.U.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Complex Perianal Fistula focused on measuring Complex perianal fistula, Crohn disease, Adipose-derived stem cells, Liposuction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Vienna
  • Academic Medical Center
  • Hospital Germans Trias i Pujol
  • Hospital de Sagunto
  • Hospital Reina Sofia
  • Complejo Hospitalario de León
  • Hospital Universitario de la Princesa
  • Hospital Gregorio Marañón
  • Hospital Ramón y Cajal
  • Hospital Puerta de Hierro
  • Hospital Clínico San Carlos
  • Complejo Hospitalario de Pontevedra

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

ASCs

Placebo

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Percentage of subjects in whom the external openings of the treated perianal fistula have closed
Changes over time in the Perianal Disease Activity Index
Changes over time in the Crohn's Disease Activity Index
Changes over time in the MRI Score of Severity (MSS)
Quality of life assessment using the SF-36 questionnaire
Percentage of subjects for whom surgery is avoided
Adverse events
Clinically relevant variations in vital signs
Clinically relevant variations in laboratory tests

Full Information

First Posted
June 21, 2011
Last Updated
April 10, 2019
Sponsor
Tigenix S.A.U.
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1. Study Identification

Unique Protocol Identification Number
NCT01378390
Brief Title
Safety and Efficacy of Adipose-Derived Stem Cells to Treat Complex Perianal Fistulas Patients With Crohn's Disease
Acronym
FATT
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Terminated
Why Stopped
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.
Study Start Date
December 2008 (undefined)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
February 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tigenix S.A.U.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Complex Perianal Fistula, Crohn Disease
Keywords
Complex perianal fistula, Crohn disease, Adipose-derived stem cells, Liposuction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ASCs
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Sham Comparator
Arm Description
Instillation of saline solution into the fistulous tract, following identical tract preparation process as for the investigational treatment group.
Intervention Type
Drug
Intervention Name(s)
Expanded autologous adipose-derived adult stem cells (eASCs)
Other Intervention Name(s)
Cx401 (company code), Ontaril®
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Normale saline solution
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of subjects in whom the external openings of the treated perianal fistula have closed
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Percentage of subjects in whom the external openings of the treated perianal fistula have closed
Time Frame
12 weeks
Title
Changes over time in the Perianal Disease Activity Index
Time Frame
4, 10, 12, 16, 22 and 24 weeks
Title
Changes over time in the Crohn's Disease Activity Index
Time Frame
10 and 22 weeks
Title
Changes over time in the MRI Score of Severity (MSS)
Time Frame
12 and 24 weeks
Title
Quality of life assessment using the SF-36 questionnaire
Time Frame
12 and 24 weeks
Title
Percentage of subjects for whom surgery is avoided
Time Frame
24 weeks
Title
Adverse events
Time Frame
4, 10, 12, 16, 22 and 24 weeks
Title
Clinically relevant variations in vital signs
Time Frame
4, 10, 12, 16, 22 and 24 weeks
Title
Clinically relevant variations in laboratory tests
Time Frame
4, 10, 12, 16, 22 and 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Damián García-Olmo, MD
Organizational Affiliation
General Surgery Department, Hospital Universitario La Paz
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Vienna
City
Vienna
Country
Austria
Facility Name
Academic Medical Center
City
Amsterdam
Country
Netherlands
Facility Name
Hospital Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital de Sagunto
City
Sagunto
State/Province
Valencia
ZIP/Postal Code
46520
Country
Spain
Facility Name
Hospital Reina Sofia
City
Córdoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Complejo Hospitalario de León
City
Léon
ZIP/Postal Code
24071
Country
Spain
Facility Name
Hospital Universitario de la Princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Hospital Gregorio Marañón
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Puerta de Hierro
City
Madrid
ZIP/Postal Code
28035
Country
Spain
Facility Name
Hospital Clínico San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Complejo Hospitalario de Pontevedra
City
Pontevedra
ZIP/Postal Code
36001
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
12756590
Citation
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.
Results Reference
background
PubMed Identifier
15933795
Citation
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.
Results Reference
background
PubMed Identifier
18696086
Citation
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.
Results Reference
background
PubMed Identifier
18694359
Citation
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.
Results Reference
background

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

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