AlloGeneic Human Mesenchymal Stem Cells (hMSC) in PAtients With FistuLizing Crohn's Disease Via PErifistula iNjEctions (GALENE) (GALENE)

This is an interventional treatment trial for Crohn's Disease Read More

Inclusion Criteria:

1. Provide written informed consent.
2. Male and Female subjects ≥ 18 years of age at the time of signing the Informed Consent Form.
3. Subjects with Fistulizing Crohn´s disease with complex perianal fistula, multiple perianal fistulas, or rectovaginal fistula(s). The complex perianal fistula is defined as a trans-sphincteric, supra-sphincteric or an extra-sphincteric tract. Patients with multiple fistulas, "horseshoe" fistula," or any fistula with fecal incontinence as a result of the Crohn's disease itself or because of previous anal fistula surgery that cannot have more surgery are also eligible.
4. If drainage of abscess is needed, it should be done 2 or more weeks prior to onset of therapy.
5. Have had Crohn's Disease (CD) diagnosed at least 6 months prior to enrollment based on clinical, endoscopic, anatomic/pathologic and/or radiologic criteria.
6. Have a CDAI score <350.
7. During the course of the subject's Crohn's disease (CD), subject must have received anti-Tumor Necrosis Factor (TNF) agents or immunomodulators which did not heal the CD fistulas. If anti-TNFs or immunomodulators are contraindicated or led to adverse events, patients must have failed conservative therapy with antibiotics, or setons, or surgical intervention.

8. Subject who are currently receiving anti-TNFs, antibiotics, 5-aminosalicylic acid, azathioprine, 6-mercaptopurine, methotrexate, prednisone, or any similar drugs at the time of enrollment as long as the following criteria are met:

   1. The patient must have been on the anti-TNF for at least 4 months
   2. The dose of 5-aminosalicylic acid (5-ASA) must have been stable for at least 4 weeks prior to enrollment.
   3. The dose of steroids must have been stable for at least 2 weeks prior to enrollment.
   4. The dose of antibiotics must have been stable for at least 2 weeks prior to enrollment.
   5. The dose of immunomodulators (for example, azathioprine, 6-mercaptopurine, or methotrexate) must have been stable for at least 8 weeks prior to enrollment and the subject on therapy for at least three months prior to enrollment
9. Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements

Exclusion Criteria:

In order to participate in this study, a patient Must Not:

1. Have a known, serious radiographic contrast allergy (gadolinium in particular)
2. Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet values < 100,000/ul without another explanation.
3. Have liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the Upper limit normal.
4. Have a coagulopathy (International Normalized ratio (INR) > 1.3) not due to a reversible cause (i.e., Coumadin). Patients on Coumadin will be withdrawn 5 days before the procedure and confirmed to have an INR < 1.3. Patients who cannot be withdrawn from Coumadin will be excluded from enrollment.
5. Bone marrow dysfunction, as evidenced by a 20% or more deviation from normal hematocrit, white blood cell count or platelet values without another explanation.
6. Be an organ transplant recipient.
7. Clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
8. Non-cardiac condition that limits lifespan to < 1 year.
9. Patients with a highly active luminal CD, i.e., if they meet any of the following criteria: - Presence of severe proctitis (prominent friability, spontaneous bleeding, multiple erosions, deep ulcers) or very active luminal disease that requires immediate treatment, revealed by colonoscopy.
10. Have anal dysplasia
11. Patients that have received radiation to the pelvic/perianal area.
12. Presence of abscess or other collections not drained (revealed by baseline radiologic study).
13. Presence of setons unless they are removed before treatment beginning.
14. Rectal and/ or anal stenosis that cannot be adequately evaluated for dysplasia by Examination under anesthesia or endoscopy.
15. Need surgery in the perianal region for reasons other than fistulas at inclusion or within 16 weeks after treatment administration.
16. Had a stable dose of an anti-TNF agent within the past 8 weeks before the cell treatment administration.
17. Taking tacrolimus or cyclosporine and not on a stable maintenance dose for 2 weeks before the start of scheduled interventions.
18. Have a history of alcohol or other addictive substances abuse within 6 months before inclusion.
19. Severe uncontrolled diseases (chronic renal failure, cardiovascular, pulmonary or any systemic disease).
20. Any type of medical or psychiatric disease which are considered as exclusion criteria, in the investigator's opinion.
21. Subjects with congenital or acquired immunodeficiency.
22. Positive serology for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV), Human papillomavirus (HPV) or Herpes Virus.
23. Had major surgery or serious traumatism within 6 weeks of enrollment.
24. Impossibility of doing an radiological exploration (reaction to contrast material, pacemakers, claustrophobia, etc.)
25. Have hypersensitivity to dimethyl sulfoxide (DMSO)
26. Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
27. Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female patients must undergo a blood or urine pregnancy test at screening and within 36 hours prior to injection.