Complex Perianal FistulaPhase 3FATTNCT01378390
Safety and Efficacy of Adipose-Derived Stem Cells to Treat Complex Perianal Fistulas Patients With Crohn's Disease
A Phase 3 study testing Expanded autologous adipose-derived adult stem cells (eASCs) in people with Complex Perianal Fistula and Crohn Disease, run by Tigenix S.A.U. at 12 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Complex Perianal Fistula, Crohn Disease
- What is being tested?
- Expanded autologous adipose-derived adult stem cells (eASCs)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 12 sitesin 3 countries
- Study dates
- Dec 2008to Feb 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 25Show fewer
- 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
Trial locations and contacts
12 sites in 3 countries.
12 sites in 3 countries
Spain10 sites
Hospital Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Reina Sofia
Córdoba, 14004
Complejo Hospitalario de León
Léon, 24071
Hospital Universitario de la Princesa
Madrid, 28006
Hospital Gregorio Marañón
Madrid, 28007
Hospital Ramón y Cajal
Madrid, 28034
Hospital Puerta de Hierro
Madrid, 28035
Hospital Clínico San Carlos
Madrid, 28040
Complejo Hospitalario de Pontevedra
Pontevedra, 36001
Hospital de Sagunto
Sagunto, Valencia, 46520
About this study
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
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.
Read the 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.
- Conditions
- Complex Perianal Fistula, Crohn Disease
- Being tested
- Expanded autologous adipose-derived adult stem cells (eASCs), Placebo
- Keywords
- Complex perianal fistula, Crohn disease, Adipose-derived stem cells, Liposuction
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Expanded autologous adipose-derived adult stem cells (eASCs)Drug
Also called Cx401 (company code), Ontaril®
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.
PlaceboDrug
Also called Normale saline solution
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of subjects in whom the external openings of the treated perianal fistula have closed
Measured: 24 weeks
Secondary outcomes (9)
Percentage of subjects in whom the external openings of the treated perianal fistula have closed
Measured: 12 weeks
Changes over time in the Perianal Disease Activity Index
Measured: 4, 10, 12, 16, 22 and 24 weeks
Changes over time in the Crohn's Disease Activity Index
Measured: 10 and 22 weeks
Changes over time in the MRI Score of Severity (MSS)
Measured: 12 and 24 weeks
Quality of life assessment using the SF-36 questionnaire
Measured: 12 and 24 weeks
Percentage of subjects for whom surgery is avoided
Measured: 24 weeks
Adverse events
Measured: 4, 10, 12, 16, 22 and 24 weeks
Clinically relevant variations in vital signs
Measured: 4, 10, 12, 16, 22 and 24 weeks
Clinically relevant variations in laboratory tests
Measured: 4, 10, 12, 16, 22 and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2011 (estimated)
- Study startDec 2008
- Primary completionFeb 2010
- Study completionFeb 2010
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Complex Perianal FistulaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tigenix S.A.U.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Damián García-Olmo, MD, Principal investigator, General Surgery Department, Hospital Universitario La Paz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01378390
- Sponsor's protocol ID
- CX-401/FATT2
- Other IDs
- EudraCT: 2008-004286-25
- Acronym
- FATT
- Status last verified
- Apr 2019
- First submitted
- 21 Jun 2011
- Last updated
- 12 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 12756590Garcia-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.
PubMed 15933795Garcia-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.
PubMed 18696086Garcia-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.
PubMed 18694359
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01378390
- Acronym / sponsor ID
- FATT / CX-401/FATT2
- Conditions
- Complex Perianal Fistula, Crohn Disease
- Keywords
- Complex perianal fistula, Crohn disease, Adipose-derived stem cells, Liposuction
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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.
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Tigenix S.A.U.Industry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- Feb 2010 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 22 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ASCs | Experimental | Drug: Expanded autologous adipose-derived adult stem cells (eASCs)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. |
| Placebo | Sham comparator | Drug: PlaceboInstillation of saline solution into the fistulous tract, following identical tract preparation process as for the investigational treatment group. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Expanded autologous adipose-derived adult stem cells (eASCs)Also: Cx401 (company code), Ontaril®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. | Drug | ASCs |
| PlaceboAlso: Normale saline solutionAdministration 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. | Drug | Placebo |
Primary outcome
Percentage of subjects in whom the external openings of the treated perianal fistula have closed
Time frame: 24 weeks
9 secondary outcomes
Percentage of subjects in whom the external openings of the treated perianal fistula have closed
Time frame: 12 weeks
Changes over time in the Perianal Disease Activity Index
Time frame: 4, 10, 12, 16, 22 and 24 weeks
Changes over time in the Crohn's Disease Activity Index
Time frame: 10 and 22 weeks
Changes over time in the MRI Score of Severity (MSS)
Time frame: 12 and 24 weeks
Quality of life assessment using the SF-36 questionnaire
Time frame: 12 and 24 weeks
Percentage of subjects for whom surgery is avoided
Time frame: 24 weeks
Adverse events
Time frame: 4, 10, 12, 16, 22 and 24 weeks
Clinically relevant variations in vital signs
Time frame: 4, 10, 12, 16, 22 and 24 weeks
Clinically relevant variations in laboratory tests
Time frame: 4, 10, 12, 16, 22 and 24 weeks
Results and safety
The study was stopped early (reason given: 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.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2019.
- Background: PubMed 12756590Garcia-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.
- Background: PubMed 15933795Garcia-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.
- Background: PubMed 18696086Garcia-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.
- Background: PubMed 18694359Garcia-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Damián García-Olmo, MD principal investigator
General Surgery Department, Hospital Universitario La Paz
12 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Expanded autologous adipose-derived adult stem cells (eASCs) in people with Complex Perianal Fistula and Crohn Disease, run by Tigenix S.A.U. at 12 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Spain, Austria, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: 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.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of subjects in whom the external openings of the treated perianal fistula have closed (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01378390, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2019.