A clinical research study of an investigational new drug to treat perianal fistulas in patients with Crohn’s disease (CD).

• Register: EUCTR
• Last refreshed on: 13 May 2024
• Main ID: EUCTR2017-000725-12-ES
• Date of registration: 06/06/2017
• Prospective Registration: Yes
• Primary sponsor: TiGenix, S.A.U.
• Public title: A clinical research study of an investigational new drug to treat perianal fistulas in patients with Crohn’s disease (CD).
• Scientific title: A phase III, randomized, double blind, parallel group, placebo controlled, international, multicentre study to assess efficacy and safety of Cx601, adult allogeneic expanded adipose-derived stem cells (eASC), for the treatment of complex perianal fistula(s) in patients with Crohn’s disease over a period of 24 weeks and a follow-up period up to 52 weeks. ADMIRE-CD II study.
• Date of first enrolment: 26/07/2017
• Target sample size: 326
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000725-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Poland, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Clinical Operations
• Affiliation: TiGenix, S.A.U.

• Name: Clinical Operations
• Affiliation: TiGenix, S.A.U.

Key inclusion & exclusion criteria

Inclusion criteria:
(1) Signed informed consent
(2) Patients of either gender = 18 years and =75 years of age
(3) Patients with Crohn’s Disease (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, assessed by clinical examination and central reading of pelvic MRI. 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 less than 14 at Screening, AND
2. a colonoscopy documenting the absence of ulcers larger than 0.5cm in the colonic mucosa: If colonoscopy data are not available within 6 months prior to Screening: a Simple Endoscopic Score for CD (SES-CD) less or equal to 6 with absence of rectal ulcers larger than 0.5cm must be documented in a colonoscopy performed at Screening before randomization. If colonoscopy data are available within 6 months prior to Screening, the following must be documented, otherwise a new colonoscopy (as above) will be mandatory: the absence of ulcers larger than 0.5cm in the colonic mucosa AND the improvement or no worsening in abdominal pain and/or in the diarrhea, sustained for one week or more, since the last colonoscopy was performed in the clinical records until Screening visit AND No hemoglobin decrease greater than 2.0 g/dl or an unexplained rising C-reactive protein (CRP), greater than 5.0 mg/l to a concentration above the referenced upper limit of normality (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 biologic therapy dose regimen since the last endoscopy up to Screening visit.
(6) Patients 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 chorionic gonad
Exclusion criteria:
(1) Concomitant rectovaginal or rectovesical fistula(s)
(2) Patient naïve to prior specific medical treatment for perianal complex 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 that make impossible to follow the surgical protocol
(5) Patient with diverting stomas
(6) Active, uncontrolled infection requiring parenteral antibiotics
(7) Patient with ongoing systemic or rectal steroids for CD in the last 2 weeks prior to Screening visit
(8) Patients with major alteration on any of the following laboratory tests or increased risk for the surgical procedure:
a. Serum creatinine levels >1.5 upper limit of normality (ULN)
b. Total bilirubin >1.5 ULN (unless predominantly non-conjugated due to documented history of Gilbert’s syndrome)
c. AST/ALT >3.0 ULN
d. Hemoglobin <10.0 g/dL
e. Platelets <75.0 x109/L
f. Albuminemia < 3.0 g/dL
(9) Suspected or documented infectious enterocolitis within two 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) Patients with primary sclerosing cholangitis
(13) Patients 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 patients known to be HIV carriers
(15) Known allergies or hypersensivity to penicillin or aminoglycosides; DMEM (Dulbecco Modified Eagle’s Medium); bovin serum; local anaesthetics or gadolinium (MRI contrast)
(16) Contraindication to MRI scan (e.g., due to the presence of pacemakers, hip replacements or severe claustrophobia)
(17) Major surgery or severe trauma within 6 months prior to Screening visit
(18) Pregnant or breastfeeding women
(19) Patients who do not wish to or cannot comply with study procedures
(20) Patients currently receiving, or having received any investigational drug for CD or the perianal fistula(s) within 3 months prior to Screening visit
(21) Patients previously treated with Cx601 or other allogeneic stem-cell therapy cannot be enrolled into this clinical study
(22) Surgery of one or more segments of the colon or terminal ileum within 3 months prior to Screening visit
(23) Patients 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 inclusion in the study, or for whom such major surgery is foreseen in this region in the 24 weeks following treatment administration at the time of screening
(24) Contraindication to the anaes

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Perianal fistulising Crohn´s disease
MedDRA version: 20.0 Level: PT Classification code 10002156 Term: Anal fistula System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: Expanded human allogenic mesenchymal adult stem cells extracted from adipose tissue
Product Code: Cx601
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: To be determined
Current Sponsor code: Allogenic eASCs
Other descriptive name: Expanded human allogenic mesenchymal adult stem cells extracted from adipose tissue (eASCs)
Concentration unit: Other
Concentration type: equal
Concentration number: 5000000-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intralesional use

Primary Outcome(s)

Primary end point(s): The primary endpoint at Week 24 is defined to be the Combined Remission of complex perianal fistula(s), defined as the clinical assessment by Week 24 of closure of all treated external openings that were draining at baseline 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 by Week 24.

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 and safety of Cx601 as compared to placebo in clinical parameters and time-related endpoints at Weeks 24 and 52, and to evaluate how many patients with Combined Remission at Week 24 have sustained remission at Week 52 and those who relapse by Week 52.

Timepoint(s) of evaluation of this end point: at week 24

Secondary Outcome(s)

Secondary end point(s): Efficacy at Week 24
• KEY: Clinical Remission at Week 24, defined as closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed at Week 24.
• KEY: Response at Week 24, defined as closure of at least 50% of all treated external openings that were draining at baseline, despite gentle finger compression, as clinically assessed at Week 24.
• Time to Clinical Remission by Week 24 (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).
• Time to Response by Week 24 (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).
Efficacy at Week 52
• Combined Remission of perianal fistula(s), defined as the clinical assessment at Week 52 of closure of all treated external openings that were draining at baseline, despite gentle finger compression, and absence of collection(s) >2 cm (in at least 2 dimensions) confirmed by blinded central MRI assessment at Week 52.
• Clinical Remission defined as closure of all treated external openings that were draining at baseline, despite gentle finger compression, as clinically assessed at Week 52.
• Response defined as closure of at least 50% of all treated external openings that were draining at baseline, despite gentle finger compression, as clinically assessed at Week 52.
• Time to Clinical Remission by Week 52 (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).
• Time to Response by Week 52 (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).
• Relapse by Week 52 defined in patients with Combined Remission by Week 24, as reopening of any of the treated external openings with active drainage as clinically assessed or the presence of collection(s) >2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by blinded central MRI assessment by Week 52.

Timepoint(s) of evaluation of this end point: at 24 and 52 weeks after the treatment

Secondary ID(s)

2017-000725-12-CZ

Cx601-0303

Source(s) of Monetary Support

TiGenix S.A.U.

Ethics review

Status: Approved
Approval date: 26/07/2017
Contact: