Perianal fistulising Crohn´s disease MedDRA version: 20.0 Level: PT Classification code 10002156 Term: Anal fistula System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Sponsors
TiGenix, S.A.U.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) Signed informed consent (2) Subjects of either gender = 18 years and =75 years of age (3) Subjects with CD diagnosed at least 6 months prior to Screening visit in accordance with accepted clinical, endoscopic, histological and/or radiological criteria (4) Presence of complex perianal fistula(s) with a maximum of 2 internal openings and a maximum of 3 external openings based on assessment; a central reading of a locally performed contrast enhanced (gadolinium) pelvic MRI will be perfomed to confirm location of the fistula and potential associated perianal abscess(es). Fistula(s) must have been draining for at least 6 weeks prior to Screening visit. Actively draining simple subcutaneous fistula(s), at the time of Screening visit, are not allowed in this study. A complex perianal fistula is defined as a fistula that meets one or more of the following criteria: • High inter-sphincteric, high trans-sphincteric, extra-sphincteric or supra-sphincteric • Presence of = 2 external openings • Associated perianal abscess(es). Note: Abscesses that are larger than 2 cm in at least 2 dimensions on MRI must be confirmed to have been drained adequately by the surgeon during the preparation curettage in order to be eligible. (5) Clinically controlled, non active or mildly active CD, during the last six months prior to Screening visit with: 1. a PRO-2 score 2.0 g/dL or an unexplained rising C-reactive protein (CRP) >5.0 mg/L to a concentration above the referenced ULN (unless the rise is due to a known process other than luminal Crohn's Disease), since the last colonoscopy was performed as compared to results during the Screening visit AND no initiation or intensification of treatment with corticosteroids, immunosuppressants or mAbs dose regimen since the last endoscopy up to Screening visit. (6) Subjects whose perianal fistulas were previously treated and have shown an inadequate response (absence of closure of part or all fistula tracts, or new fistula during induction treatment) or a loss of response (fistula relapse during maintenance treatment after initial fistula closure) while they were receiving either an immunosuppressive agent or TNF-a antagonist or vedolizumab or ustekinumab, or having documented intolerance (occurrence, at any time, of an unacceptable level of treatment-related side effects that makes necessary treatment discontinuation) to any of these treatments administered at least at approved or recommended doses during the minimum period mentioned: -Immunosuppressive agents -TNFa antagonists - Anti-integrin - Anti-IL-12/23 (7) Women of childbearing potential (WCBP) must have negative serum pregnancy test at Screening (sensitive to 25 IU human chor
Exclusion criteria
Exclusion criteria: (1) Concomitant rectovaginal or rectovesical fistula(s) (2) Subject naïve to prior specific medical treatment for complex perianal fistula(s) including IS or anti-TNFs. (3) Presence of a perianal collection > 2 cm in at least two dimensions on the central reading MRI at Screening visit that was not adequately drained as confirmed by the surgeon during the preparation procedure (week -3 to day 0) (4) Severe rectal and/or anal stenosis and/or severe proctitis (defined as the presence of large [>0.5 cm] ulcers in the rectum) that make it impossible to follow the Surgery Procedure Manual. (5) Subject with diverting stomas. (6) Active, uncontrolled infection requiring parenteral antibiotics. (7) Subject with ongoing systemic or rectal steroids for CD in the last 2 weeks prior to Preparation visit. (8) Subject with major alteration on any of the following laboratory tests or increased risk for the surgical procedure: a. Serum creatinine levels >1.5 times the ULN b. Total bilirubin >1.5 times the ULN (unless predominantly nonconjugated due to documented history of Gilbert's syndrome) c. AST/ALT >3.0 times the ULN d. Hemoglobin <10.0 g/dL e. Platelets <75.0 x 109/L f. Albuminemia <3.0 g/dL (9) Suspected or documented infectious enterocolitis within 2 weeks prior to Screening visit. (10) Any prior invasive malignancy diagnosed within the last 5 years prior to Screening visit. Patients with basal-cell carcinoma of the skin completely resected outside the perineal region can be included. (11) Current or recent (within 6 months prior to the Screening visit) history of severe, progressive, and/or uncontrolled hepatic, haematological, gastrointestinal (other than CD), renal, endocrine, pulmonary, cardiac, neurological or psychiatric disease that may result in patients increased risk from study participation and/or lack of compliance with study procedures (12) Subjects with primary sclerosing cholangitis (13) Subjects with known chronically active hepatopathy of any origin, including cirrhosis and patients with persistent positive HBV surface antigen (HBsAg) and quantitative HBV polymerase chain reaction (PCR), or positive serology for HCV and quantitative HCV PCR within 6 months prior to Screening. (14) Congenital or acquired immunodeficiencies, including subjects known to be HIV carriers, (15) Known allergies or hypersensivitivity to penicillin or aminoglycosides; DMEM; bovine serum; local anaesthetics or gadolinium (MRI contrast). (16) Contraindication to MRI scan (e.g., due to the presence of pacemaker, hip replacement or severe claustrophobia). (17) Severe trauma within 6 months prior to Screening visit. (18) Pregnant or breastfeeding women. (19) Subjects who do not wish to or cannot comply with study procedures. (20) Subjects currently receiving, or having received any investigational drug within 3 months prior to Screening visit. (21) Subjects previously treated with Cx601 or other allogeneic stemcell therapy cannot be enrolled into this clinical study. (22) Any major surgery of the GI tract (including one or more segments of the colon or terminal ileum) within 6 months prior to screening or any minor surgery of the GI tract within 3 months prior to screening. (23) Subjects who had local perianal surgery other than drainage for the fistula within 6 months prior to the Screening visit, or those who may need surgery in the perianal region for reasons other than fistulas at the time of inclu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the Combined Remission of complex perianal fistula(s), defined as the clinical assessment at Week 24 of closure of all treated external openings that were draining at baseline despite gentle finger compression, and absence of collections >2 cm (in at least 2 dimensions) confirmed by blinded central MRI assessment at Week 24.;Secondary Objective: - To evaluate the efficacy of Cx601 as compared to placebo in clinical remission at Week 24 and in time to clinical remission (weeks). - To evaluate the efficacy and safety of Cx601 as compared to placebo in other clinical and time-to-event related endpoints at Weeks 24 and 52 ;Primary end point(s): Proportion of subjects who achieve combined remission at Week 24 after IMP administration, where combined remission is defined as: - The closure of all treated external openings that were draining atmbaseline despite gentle finger compression AND - Absence of collection(s) >2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by blinded central MRI assessment.;Timepoint(s) of evaluation of this end point: at week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficacy Endpoints - Proportion of subjects who achieve clinical remission at Week 24 after IMP administration, where clinical remission is defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression. - Time to clinical remission (weeks) assessed at Week 24, defined as the time from treatment start to first visit with closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed. Subjects who do not achieve clinical remission by Week 24 will be censored at that visit. Other Secondary Efficacy Endpoints - Proportion of subjects who achieve clinical response at Week 24 after IMP administration, where clinical response is defined as closure of at least 50% of all treated external openings that were draining at baseline despite gentle finger compression. - Time to clinical response (weeks) assessed at Week 24, defined as the time from treatment start to first visit with closure of at least 50% of all treated external openings that were draining at baseline, despite gentle finger compression, as clinically assessed. Subjects who do not achieve clinical response by Week 24 will be censored at that visit. - Proportion of subjects who achieve combined remission at Week 52 after IMP administration, where combined remission is defined as: a) The closure of all treated external openings that were draining at baseline despite gentle finger compression, AND b) Absence of collection(s) >2 cm (in at least 2 dimensions) confirmed by blinded central MRI assessment. - Proportion of subjects who achieve clinical remission at Week 52 after IMP administration, where clinical remission is defined as closure of all treated external openings that were draining at baseline despite gentle finger compression. - Proportion of subjects who achieve clinical response at Week 52 after IMP administratio | — |
Countries
Belgium, Canada, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Poland, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Operations
TiGenix, S.A.U.
Outcome results
None listed