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.

• Register: EUCTR
• Last refreshed on: 22 May 2017
• Main ID: EUCTR2011-006064-43-DE
• Date of registration: 17/02/2012
• Prospective Registration: Yes
• Primary sponsor: TiGenix S.A.U.
• Public title: 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.
• Scientific title: A phase III, randomised, double blind, parallel group, placebo controlled, multicentre study to assess efficacy and safety of expanded allogeneic adipose-derived stem cells (eASCs) for the treatment of perianal fistulising Crohn's disease over a period of 24 weeks and an extended follow-up period up to 104 weeks. ADMIRE-CD study.
• Date of first enrolment: 27/09/2012
• Target sample size: 208
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-006064-43
• 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

Austria, Belgium, France, Germany, Israel, Italy, Netherlands, Spain

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 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 and 104
weeks, it is required the previous participation in the CX601-0302 study,
having completed 24 and 52 weeks respectively. Patients should have
signed the information consent for the extension follow-up period up to
52 and 104 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 enroled 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.



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

Health Condition(s) or Problem(s) studied

Perianal fistulising Crohn´s disease
MedDRA version: 17.1 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: Allogenic eASCs 5 million cells/ml suspension for injection. CX601
Product Code: Cx601
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Not applicable
Current Sponsor code: Allogenic eASCs
Other descriptive name: Expanded human allogenic mesenchymal adult stem cells extracted from adipose tissue (eASCs)
Concentration unit: U/ml unit(s)/millilitre
Concentration type: equal
Concentration number: 5000000 -
Pharmaceutical form of the placebo: Suspension for injection
Route of administration of the placebo: Intralesional use

Primary Outcome(s)

Secondary Objective: There are no secondary objectives

Main Objective: Evaluate the efficacy and safety of eASCs compared to placebo for the
treatment of perianal fistulising Crohn's disease over a 24-week and an
extended follow-up period up to 104 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).

Timepoint(s) of evaluation of this end point: 24 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: at 24, 52 and 104 weeks after the treatment

Secondary end point(s): Secondary endpoints
Efficacy analysis at week 24
• KEY: Clinical Remission defined as closure of all treated external
openings that were draining at baseline despite gentle finger
compression, as clinically assessed by week 24
• KEY: Response defined as closure of at least 50% of all treated
external openings that were draining at baseline, as clinically assessed
by week 24
• Time to Clinical Remission by week 24 (defined as time from treatment
start to first visit with closure of all treated external openings that were
draining at baseline, as clinically assessed)
• Time to Response by week 24 (defined as time from treatment start to
first visit with closure of at least 50% of all treated external openings
that were draining at baseline, as clinically assessed)
• Relapse by week 24 defined, in patients with Clinical Remission at
previous visit, as reopening of any of the treated external openings with
active drainage as clinically assessed, or the development of a perianal
collection > 2 cm of the treated perianal fistulas confirmed by centrally
blinded MRI assessment by week 24)
• Time to Relapse by week 24 in patients with Clinical Remission
(defined as time from Clinical Remission to first visit with reopening of
any of the treated external openings with active drainage as clinically
assessed, or the development of a perianal collection > 2 cm of the
treated perianal fistulas confirmed by centrally blinded MRI assessment
by week 24)
• Severity of the perianal Crohn's disease up to week 24, assessed with
the Perianal Disease Activity Index (PDAI)
• Quality of Life (QoL) up to week 24 assessed by the Inflammatory
Bowel Disease Questionnaire (IBDQ)
• CDAI score up to week 24
• Van Assche score up to week 24
Efficacy analysis at week 52:
• Combined Remission of perianal fistulising Crohn's disease defined as
the clinical assessment of closure of all the treated external openings
that were draining at baseline
despite gentle finger compression at week 52, and absence of collections
> 2 cm of the treated perianal fistulas confirmed by centrally blinded
MRI assessment by week 52
• Clinical Remission defined as the 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, as clinically assessed at week 52
• Time to Combined Remission by week 52 (defined as time from
treatment start to first visit with clinical assessment of closure of all the
treated external openings that were draining at baseline despite gentle
finger compression at week 52, and absence of collections > 2 cm of the
treated perianal fistulas confirmed by centrally blinded MRI assessment
by week 52)
• Time to Clinical Remission by week 52 (defined as time from treatment
start to first visit with closure of all treated external openings that were
draining at baseline, as clinically assessed)
• Time to Response by week 52 (defined as time from treatment start to
first visit with closure of at least 50% of all treated external openings
that were draining at baseline,
as clinically assessed)
• Relapse by week 52 in patients with Combined Remission at week 24,
defined as reopening of any of the treated external openings with active
drainage as clinically assessed or the development of a perianal
collection > 2 cm of the treated perianal fistulas confirmed by centrally
blinded MRI assessment by 52 weeks
• Time to Relapse by week 52 in patients with Combined Remission at
week 24 (defined as time from Combined Remission to first visit with
reopening of any of the treated external openings with active drainage
as clinically assessed, or the development of a perianal collection > 2 cm
of the treated perianal fistulas confirmed by centrally blinded MRI
assessment by week 52
• Severity of the perianal Crohn's disease up to week 52, assessed with
PDAI
• Quality of Life (QoL) up to week 52 assessed by IBQD
• CDAI score up to week 52
• Van Assche score up to week 52
Efficacy analysis at week 104:
• Clinical Remission of perianal fistulising Crohn's disease defined as the
clinical assessment of closure of all treated external openings that were
draining at baseline despitegentle finger compression at week 104
• Relapse by week 104 in patients with Combined Remission at week 52,
defined as reopening of any of the treated external openings with active
drainage as clinically assessed
• Time to Relapse by week 104 in patients with Combined Remission at
week 52 (defined as time from Combined Remission to first visit with
reopening of any of the treated external openings with active drainage
as clinically assessed)
• Severity of the perianal Crohn's disease, assessed with PDAI up to
week 104
• Quality of Life (QoL) assessed by the IBQD up to week 104
• CDAI score up to week 104

Secondary ID(s)

Cx601-0302

Source(s) of Monetary Support

TiGenix, S.A.U.