Study to assess efficacy and safety of stem cells derived from allogeneic adipose tissue for the treatment of perianal fistulas in patients with Crohn's disease.

Phase 1

• Conditions: Perianal fistulising Crohn´s disease; MedDRA version: 16.0Level: PTClassification code 10002156Term: Anal fistulaSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2011-006064-43-NL
• Lead Sponsor: TiGenix, S.A. Unipersonal

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-07-05
• Study Completion: 2017-02-10
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 212

Inclusion Criteria

(1)Signed informed consent*
(2)Patients with Crohn’s Disease (CD) diagnosed at least 6 months earlier in accordance with accepted clinical, endoscopic, histological and/or radiologic criteria
(3)Presence of complex perianal fistulas with a maximum of 2 internal openings and a maximum of 3 external openings, assessed by clinical assessment and MRI. Fistula must have been draining for at least 6 weeks prior to the inclusion.
A complex perianal fistula is defined as a fistula that met one or more of the following criteria during its evolution:
•High inter-sphincteric, trans-sphincteric, extra-sphincteric or supra-sphincteric
•Presence of = 2 external openings (tracts)
•Associated collections
(4)Non-active or mildly active luminal CD defined by a CDAI = 220
(5)Patients of either sex aged 18 years or older
(6)Good general state of health according to clinical history and a physical examination
(7)For women of a childbearing age, they must have 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
*To participate in the extension follow-up period up to 52 weeks, it is required the previous participation in the Cx601-0302 study, having completed 24 weeks within it, or alternatively having the early-termination visit done. Patients should have signed the informed consent for the extension follow-up period up to 52 weeks.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 139
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 69

Exclusion Criteria

(1)Presence of dominant luminal active Crohn’s disease requiring immediate therapy
(2)CDAI >220
(3)Concomitant rectovaginal fistulas
(4)Patient naïve to specific treatment for perianal fistulising Crohn’s disease including antibiotics
(5)Presence of an abscess or collections > 2 cm, unless resolved in the preparation procedure (week -3 to day 0)
(6)Presence of > 2 internal openings
(7)Presence of > 3 external openings
(8)Rectal and/or anal stenosis and / or active proctitis, if this means a limitation for any surgical procedure
(9)Patient who underwent surgery for the fistula other than drainage or seton placement
(10)Patient with diverting stomas
(11)Patient with ongoing steroid treatment or treated with steroids in the last 4 weeks
(12)Renal impairment defined by creatinine clearance below 60 ml/min calculated using Cockcroft-Gault formula or by serum creatinine = 1.5 x upper limit of normality (ULN)
(13)Hepatic impairment defined by both of the following laboratory ranges:
•Total bilirubin = 1.5 x ULN
•AST and ALT = 2.5 x ULN
(14)Known history of abuse of alcohol or other addictive substances in the 6 months prior to inclusion
(15)Malignant tumour or patients with a prior history of any malignant tumour, including any type of fistula carcinoma
(16)Current or recent history of abnormal, severe, progressive, uncontrolled hepatic, haematological, gastrointestinal (except CD), endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral disease
(17)Congenital or acquired immunodeficiencies
(18)Known allergies or hypersensivity to antibiotics including but not limited to penicillin, streptomycin, gentamicin, aminoglycosides; HSA (Human Serum Albumin); DMEM (Dulbecco Modified Eagle’s Medium); materials of bovin origin; local anaesthetics or gadolinium (MRI contrast)
(19)Contraindication to MRI scan, (e.g., due to the presence of pacemakers, hip replacements or severe claustrophobia)
(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 previously treated with eASCs can not be enrol into this clinical study
(25)Subjects who need surgery in the perianal region for reasons other than fistulas at the time of inclusion in the study, or for whom such surgery is foreseen in this region in the 24 weeks after treatment administration
(26)Contraindication to the anaesthetic procedure

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy and safety of eASCs compared to placebo for the treatment of compex fistulas in Crohn's disease over a 24-week period and an extended follow-up period up to 52 weeks.;Secondary Objective: There are no secondary objectives.;Timepoint(s) of evaluation of this end point: 24 weeks;Primary end point(s): Remission of perianal fistulising Crohn?s disease at week 24 confirmed by MRI, defined as the clinical assessment of closure of all the external openings that were draining at baseline despite gentle finger compression at week 24, confirmed by MRI as absence of collections > 2 cm of the treated perianal fistulas at 24 weeks (central blind assessment).