Randomized, single-blind, placebo controlled multicenter phase III study to assess the efficacy and safety of expanded autologous adipose-derived stem cells (eASCs) (CX-401), for treatment of complex perianal fistulas in Crohn*s disease.
- Conditions
- inflammation of intestine10018008
- Registration Number
- NL-OMON35164
- Lead Sponsor
- Cellerix S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 18
1. Signed informed consent.
2. Patients with CD diagnosed at least 12 months earlier in accordance with accepted clinical, endoscopic, anatomical/topographical and/or radiologic criteria. France and Italy only: Patients with CD diagnosed at least 12 months earlier in accordance with accepted clinical, endoscopic, anatomical/topographical and/or radiological criteria, unresponsive (treatment failure and/or intolerance and/or contraindication) to conventional treatment, including anti-TNF.
3. Presence of complex perianal fistula with up to 3 external openings, assessed by MRI. The blinded fistulae branches visible though MRI are not considered fistula tracts but branches of the main tract. A 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 associated to a complex perianal fistula.
4. Non-active or mildly active luminal CD defined by a CDAI <=220.
5. Patients of either sex aged 18 years or older. Good general state of health according to clinical history and a physical examination.
6. 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.
1. Presence of severe proctitis (prominent friability, spontaneous bleeding, multiple erosions, deep ulcers) or dominant active Crohns disease requiring immediate therapy, assessed by rectosigmoidoscopy
2. CDAI >220.
3. Presence of an abscess or collections >2 cm, unless a complete surgical debridement of the area has been performed, including drainage of the collection(s) and an MRI scan confirms absence of (residual) abscess before randomization.
4. Presence of setons. If present at screening they should be removed prior to treatment administration.
5. Presence of >3 external openings.
6. Rectal and/or anal stenosis.
7. Treatment with infliximab or any other anti-TNF agent in the 8 weeks before the cell treatment administration.
8. Patients having received adalimumab in the 4 weeks before the cell treatment adminsitration.
9. Treatment with tracrolimus or cyclosporine in the 4 weeks before the cell treatment administration.
10. HIV, HBV, HCV or treponema infection.
11. Persistent chronic bacterial infections of temporary nature as well as local infections unless succesfully treated prior liposuction, such as syphilis, brucellosis, typhus, melioidosis, q-fever, meningitis, or other.
12. Renal impairment defined by creatinine clearance below 60 ml/min calculated using Cockcroft-Gault formula (see appendix I) or the following laboratory ranges:
Total bilirubin > 1.5 x upper limit of normal (ULN)
AST and ALT > 2.5 X ULN
Serum creatinine > 1.5 ULN
13. Known history of abuse of alcohol or other addictive substances in the 6 months prior to inclusion.
14. Malignant tumor or patients with a prior history of malignant tumors.
15. Current or recent history of abnormal, severe, progressive, uncontrolled liver function, anemia, hepatic, hematological, gastrointestinal (except CD), endocrine, pulmonary, cardiac, neurological, psychiatric ,or cerebral disease.
16. Congenital or acquired immunodeficiencies.
17. Known allergies or hypersensivity to antibiotics including but not limited to penicillin, streptomycin, gentamicin, aminoglycosides; HSA; DMEM; materials of bovin origin; local anesthetics or gadolinium (MRI contrast).
18. Contraindication to MRI scan, (e.g., due to the presence of pacemakers, hip replacements or severe claustrophobia).
19. 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.
20. Major surgery or severe trauma within the previous 6 months.
21. Pregnant or breastfeeding women.
22. Patients who do not wish to or cannot comply with study procedures.
23. Patients currently receiving, or having received within 3 months prior to enrolment into this clinical study, any investigational drug.
24. Patients unlikely to comply with study procedures.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is the percentage of anti-TNF previous exposed patients<br /><br>with complete closure of their treated complex perianal fistula at Week 24.<br /><br>Complete closure of the fistula is defined as:<br /><br><br /><br>•Absence of drainage/suppuration of the fistula through the external orifice,<br /><br>either spontaneously or when applying pressure, and<br /><br>•Complete re-epithelization of the external orifice (clinical evaluation), and<br /><br>•Absence of fluid collections >2 cm directly related to the treated fistula<br /><br>tract, as measured by MRI, in the longest diameter.<br /><br><br /><br>Clinically, complete closure must be confirmed at both, the Week 24 and the<br /><br>Week 26 visit.</p><br>
- Secondary Outcome Measures
Name Time Method