E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Complex perianal fistula in perianal Crohn´s disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002156 |
E.1.2 | Term | Anal fistula |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to evaluate the efficacy of intralesional administration of eASCs (CX-401) when added to standard surgical care and drainage for the treatment of complex perianal fistulas in patients with CD. |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the safety of intralesional administration of eASC’s (CX-401) when given at baseline with a possible repeat dose at Week 12, and a follow-up period of 12 weeks. • To evaluate the effect of intrafistular administration of eASC’s (CX-401) on the incidence of complications of complex fistulas in patients with CD (such as abscesses or fluid collections) using MRI. • To compare the use of eASC’s (CX-401) with placebo with regard to the fistular relapse rate. • To obtain data regarding prevention of invasive surgical procedures and use of additional therapies. • To obtain QoL data. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
"Inflammation substudy (Biomarker Evaluation)" (only applicable at selected sites in Spain)
SUBSTUDY OBJECTIVES 1.- To determine both the frequency of the population of regulatory T cells (Treg) and the ratio Treg/Th17 in the blood of patients from FATT-2 study. This research may potentially link the frequency of Tregs in the blood of patients as an in vivo maker for Ontaril efficiency. 2.- To investigate the levels of pro-inflammatory (Th1) cytokines and compare them to the levels of anti-inflammatory (Th2) cytokines. Analysis is designed to correlate the healing of the fistula induced by the ASC treatment with cytokine levels. |
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E.3 | Principal inclusion criteria |
A patient can be included in the study if he/she meets ALL the criteria listed below: 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. Treatment failure means persistence or recurrence of fistula-related discharge despite correctly conducted induction treatment with anti-TNF antibodies with at least 3 infusions/injections. It is, however, possible to authorize inclusion of patients who do not tolerate anti-TNF antibodies (allergy) and, in consequence, have not received a complete course of anti-TNF antibody treatment. Patients to whom treatment with anti-TNF agent is contraindicated, may also be included if they fulfill other eligibility criteria. 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 human chorionic gonadotropin [hCG]). Both men and women should use appropriate birth control methods defined by the investigator. |
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E.4 | Principal exclusion criteria |
A patient cannot be included in the study if he/she meets ANY of the criteria listed below 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 administration. 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, qfever, 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percentage of anti-TNF exposed patients with complete closure of their treated complex perianal fistula at Week 24. Complete closure of the fistula is defined as: • Absence of drainage/suppuration of the fistula through the external orifice, either spontaneously or when applying pressure, and • Complete re-epithelization of the external orifice (clinical evaluation), and • Absence of fluid collections >2 cm directly related to the treated fistula tract, as measured by MRI, in the longest diameter. Clinically, complete closure must be confirmed at both, the Week 24 and the Week 26 visit. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Sub-study to investigate autoimmune response (see Protocol section 10 – 1.2 Objectives) |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Sub-study to investigate autoimmune response (see Protocol section 10 – 1.2 Objectives) |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Final study: last visit carried out. The last patient included may not need the second dose, this would mean that the last visit will correspond to a patient included previously who needs a second dose. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |