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Crohn's DiseasePhase 3ADMIRE-CDNCT01541579

Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn's Disease

A Phase 3 study testing Cx601 and Saline solution in people with Crohn's Disease, run by Tigenix S.A.U. at 52 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The current multicentre phase III study is proposed to confirm in an add-on therapy design compared to a placebo-control group, the efficacy of adipose-derived stem cells (eASCs) from healthy donors for the treatment of complex anal fistulas in patients with Crohn's disease over a 24-week period and an extended… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Crohn's Disease
What is being tested?
Cx601 and Saline solution
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
278 participants
Where
52 sitesin 8 countries
Study dates
Jul 2012to Nov 2016
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The reference population will consist of patients with perianal fistulising Crohn´s disease refractory to at least one of the following treatments: antibiotics, immunosuppressants or anti-tumor necrosis factor (TNF). Naïve patients are excluded, and those patients refractory to antibiotics will represent less than 25% of the total recruited patients.
  • All of them must comply with the following inclusion criteria:
  • Signed informed consent.
  • Patients with Crohn's Disease (CD) diagnosed at least 6 months earlier in accordance with accepted clinical, endoscopic, histological and/or radiologic criteria.
  • Presence of complex perianal fistulas with a maximum of 2 fistulas (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.
Show all 12Show fewer
  • Presence of ≥ 2 external openings (tracts).
  • Associated collections
  • Non-active or mildly active luminal CD defined by a CDAI ≤ 220.
  • Patients of either sex aged 18 years or older
  • Good general state of health according to clinical history and a physical examination.
  • 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.

Who cannot join

  • Presence of dominant luminal active Crohn's disease requiring immediate therapy.
  • CDAI >220.
  • Concomitant rectovaginal fistulas
  • Patient naïve to specific treatment for perianal fistulising Crohn's disease including antibiotics
  • Presence of an abscess or collections > 2 cm, unless resolved in the preparation procedure (week -3 to day 0).
  • Presence of > 2 fistular lesions.
Show all 28Show fewer
  • Presence of > 3 external openings.
  • Rectal and/or anal stenosis and / or active proctitis, if this means a limitation for any surgical procedure.
  • Patient who underwent surgery for the fistula other than drainage or seton placement.
  • Patient with diverting stomas
  • Patient with ongoing steroid treatment or treated with steroids in the last 4 weeks
  • 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)
  • Hepatic impairment defined by both of the following laboratory ranges:
  • Total bilirubin ≥ 1.5 x ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase(ALT) ≥ 2.5 x ULN
  • Known history of abuse of alcohol or other addictive substances in the 6 months prior to inclusion.
  • Malignant tumour or patients with a prior history of any malignant tumour, including any type of fistula carcinoma.
  • Current or recent history of abnormal, severe, progressive, uncontrolled hepatic, haematological, gastrointestinal (except CD), endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral disease.
  • Congenital or acquired immunodeficiencies.
  • Known allergies or hypersensitivity to antibiotics including but not limited to penicillin, streptomycin, gentamicin, aminoglycosides; Human Serum Albumin (HSA); Dulbecco Modified Eagle's Medium (DMEM); materials of bovine origin; local anaesthetics or gadolinium (MRI contrast).
  • Contraindication to MRI scan, (e.g., due to the presence of pacemakers, hip replacements or severe claustrophobia).
  • Major surgery or severe trauma within the previous 6 months.
  • Pregnant or breastfeeding women.
  • Patients who do not wish to or cannot comply with study procedures.
  • Patients currently receiving, or having received within 3 months prior to enrolment into this clinical study, any investigational drug.
  • Patients previously treated with eASCs can not be enrol into this clinical study.
  • 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.
  • Contraindication to the anaesthetic procedure.

Trial locations and contacts

52 sites in 8 countries.

52 sites in 8 countries

Spain15 sites

  • Hospital Clinic de Barcelona

    Barcelona

  • Hospital Universitario Reina Sofia

    Córdoba

  • Hospital Juan Ramon Jimenez

    Huelva

  • Hospital Ramón y Cajal

    Madrid, 28034

  • Fundacion Jimenez Diaz

    Madrid, 28040

  • Hospital 12 de Octubre

    Madrid

  • Hospital Clinico San Carlos

    Madrid

  • Hospital La Princesa

    Madrid

  • Hospital Universitario La Paz

    Madrid

  • Hospital de Manises

    Manises, Valencia, 46940

  • Son Espases

    Palma de Mallorca, 07010

  • Hospital de Montecelo

    Pontevedra

  • Hospital Virgen del Rocio

    Seville

  • Hospital de Sagunto

    Valencia

  • Hospital Universitario La Fe

    Valencia

Other trials in Spain

France8 sites

  • CHU d'Amiens

    Amiens, 80054

  • CHU de Bordeaux

    Bordeaux, 3300

  • CHU de Caen

    Caen, 14033

  • Hôpital Beaujon

    Clichy

  • CHRU de Lille

    Lille, 59037

  • CHU de Marseille

    Marseille, 13915

  • CHU de Nice

    Nice, 06202

  • Hôpital Saint-Louis

    Paris

Other trials in France

Italy7 sites

  • Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant'Orsola Malpighi

    Bologna

  • Azienda Ospedaliero-Universitaria Careggi

    Florence, 50134

  • Instituto Clinico Humanitas IRCCS

    Milan, 20089

  • Seconda Università degli Studi di Napoli

    Naples

  • Azienda Ospedaliera di Padova

    Padova, 35128

  • Azienda Ospedaliera San Camillo-Forlanini

    Rome, 00149

  • Università Cattolica del Sacro Cuore

    Rome, 00168

Other trials in Italy

Germany6 sites

  • Charite

    Berlin, 13353

  • Krakenhaus Walfriede

    Berlin, 14163

  • Klinikum Braunscheweig

    Braunschweig, 38126

  • Evangelisches Krankenhaus Kalk

    Cologne, 51103

  • Klinikum Frankfurt

    Frankfurt am Main, 60431

  • Klinikum Lüneburg

    Lüneburg, 21339

Other trials in Germany

Israel5 sites

  • Rambam MC

    Haifa, 31096

  • Sharee Zedek MC

    Jerusalem, 91031

  • Rabin MC

    Petah Tikva, 49100

  • Tel Aviv Sourasky MC

    Tel Aviv, 64239

  • Sheba MC

    Tel HaShomer, 52621

Other trials in Israel

Belgium4 sites

  • Hospital Oost-Limburg

    Genk, 3600

  • Gent University Hospital

    Ghent, 9000

  • Leuven University Hospital

    Leuven, 3000

  • Hospital Hartziekenhuis

    Roeselare, 8800

Other trials in Belgium

Netherlands4 sites

  • AMC

    Amsterdam

  • VUMC

    Amsterdam

  • Catharina Ziekenhuis

    Eindhoven, 5623

  • UMCU

    Utrecht

Other trials in Netherlands

Austria3 sites

  • Univ.-Klinik Innsbruck

    Innsbruck, 6020

  • Krankenhaus

    Saint Veit/Glan, 9300

  • Medizinische Universität

    Vienna, 1090

Other trials in Austria

About this study

Official title: A Phase III, Randomized, 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.

The current multicentre phase III study is proposed to confirm in an add-on therapy design compared to a placebo-control group, the efficacy of adipose-derived stem cells (eASCs) from healthy donors for the treatment of complex anal fistulas in patients with Crohn's disease over a 24-week period and an extended follow-up period up to 104 weeks.

Read the detailed description

The current multicentre phase III study is proposed to confirm in an add-on therapy design compared to a placebo-control group, the efficacy of adipose-derived stem cells (eASCs) from healthy donors for the treatment of complex anal fistulas in patients with Crohn's disease over a 24-week period and an extended follow-up period up to 104 weeks. Subject with perianal fistulising Crohn's disease will be treated with Cx601, suspension of eASCs, at a dose of 120 million cells administered by intralesional injection. The treatment of complex perianal fistulas by local application of eASCs intends to improve significantly the local conditions with very few inconveniences (ambulatory procedure) and minimal risk of possible complications (anal incontinence). Therefore, this is a new therapeutic resource that is expected to be safe and efficacious as well as is expected to improve the quality of life of the patients in this highly debilitating and chronic condition. This treatment would prevent one of the main causes of anal incontinence, would diminish recurrence of the fistula disease and would reduce drastically the significant disorders provoked by the standard fistula surgery in the patients. Indeed, patients can be discharged according to the "One Day Surgical" procedures (major ambulatory surgery).

Conditions
Crohn's Disease
Being tested
Cx601, Saline solution
Keywords
Perianal fistulising Crohn's disease.
Medical subject headings
Crohn Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cx601Other

    120 million cells administered by intralesional injection.

  • Saline solutionOther

    24 mL saline solution by intralesional injection

Study groups in NCT01541579
Study groupRoleWhat they receive
Treatment ArmExperimentalCx601 is a cell suspension in aseptic buffered solution containing human expanded adipose-derived stem cells (eASCs) of allogeneic origin in disposable vials with no preservative agents. The cells will be given at a dose of 120 million cells (5 million cells / mL) for intralesional injection.
Receives: Other: Cx601
Placebo-control groupPlacebo comparatorPlacebo (saline solution) will be given also for intralesional injection at the same quantity (volume, 24 mL) and following the same schedule.
Receives: Other: Saline solution

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Combine remission of perianal fistulising Crohn's

    Combined Remission of perianal fistulising Crohn's disease defined as the clinical assessment of closure of all treated external openings (EO) that were draining at baseline despite gentle finger compression at week 24, and absence of collections > 2 cm of the treated perianal fistulas confirmed by centrally blinded MRI assessment by week 24.

    Measured: 24 weeks

Secondary outcomes (4)

  1. Efficacy Assessment by week 24

    • Clinical Remission (CR) defined as closure of all treated EO that were draining at baseline despite gentle finger compression, as clinically assessed
    • Response defined as closure of at least 50% of all treated EO that were draining at baseline, as clinically assessed
    • Time to Clinical Remission (time from treatment start to 1st visit with closure of all treated EO as described above)
    • Time to Response (time from treatment start to 1st visit with closure of at least 50% of all treated EO as described above)
    • Relapse defined, in patients with CR at previous visit, as reopening of any of the treated EO with active drainage, or the development of a perianal collection > 2 cm of the treated perianal fistulas confirmed by centrally blinded MRI
    • Time to Relapse in patients with CR (time from CR to 1st visit with reopening of any of the treated EO as described above)
    • Severity of the perianal CD, assessed with the PDAI
    • QoL assessed by IBDQ
    • CDAI score
    • Van Assche

    Measured: 24 weeks

  2. Efficacy Assessment by week 52

    • Combined Remission of perianal fistulising Crohn's disease at week 52 (as defined for week 24)
    • 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 (as defined for week 24)
    • Time to Clinical Remission by week 52 (as defined for week 24)
    • Time to Response by week 52 (as defined for week 24)
    • Relapse by week 52 in patients with Combined Remission at week 24 (as defined for week 24)
    • Time to Relapse by week 52 in patients with Combined Remission at week 24 (as defined for week 24)
    • Severity of the perianal Crohn's disease up to week 52 assessed PDAI
    • QoL up to week 52 by the IBDQ
    • CDAI score up to week 52
    • Van Assche score up to week 52

    Measured: 52 weeks

  3. Efficacy Assessment by 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 despite gentle 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 the Perianal Disease Activity Index (PDAI) up to week 104
    • Quality of Life (QoL) assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ) up to week 104
    • CDAI score up to week 104

    Measured: 104 Weeks

  4. Safety analysis throughout the study:

    • Adverse events including: Treatment emergent Adverse Events (TEAEs), TEAEs related to study treatment, Treatment emergent Serious Adverse Events (TESAEs), TESAEs related to study treatment, TEAEs leading to study withdrawal, adverse events related to surgical procedure(s) to provide study treatment, deaths Only SAEs will be reported during the 2nd follow-up period between week 52 and week 104.
    • Physical examination
    • Vital signs
    • Laboratory tests (biochemistry, haematology, urinalysis)

    Measured: week 24, 52 and 104

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Mar 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionJul 2015
  4. Study completionNov 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
278 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01541579
Sponsor's protocol ID
Cx601-0302
Acronym
ADMIRE-CD
Status last verified
Nov 2019
First submitted
21 Feb 2012
Last updated
29 Nov 2019
Results posted
No
Data monitoring committee
No

Publications

  • Garcia-Olmo D, Gilaberte I, Binek M, D Hoore AJL, Lindner D, Selvaggi F, Spinelli A, Panes J. Follow-up Study to Evaluate the Long-term Safety and Efficacy of Darvadstrocel (Mesenchymal Stem Cell Treatment) in Patients With Perianal Fistulizing Crohn's Disease: ADMIRE-CD Phase 3 Randomized Controlled Trial. Dis Colon Rectum. 2022 May 1;65(5):713-720. doi: 10.1097/DCR.0000000000002325.

    PubMed 34890373

  • Panes J, Garcia-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Diez MC, Tagarro I, Leselbaum A, Danese S; ADMIRE CD Study Group Collaborators. Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease. Gastroenterology. 2018 Apr;154(5):1334-1342.e4. doi: 10.1053/j.gastro.2017.12.020. Epub 2017 Dec 24.

    PubMed 29277560

  • Panes J, Garcia-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Leselbaum A, Danese S; ADMIRE CD Study Group Collaborators. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial. Lancet. 2016 Sep 24;388(10051):1281-90. doi: 10.1016/S0140-6736(16)31203-X. Epub 2016 Jul 29.

    PubMed 27477896

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cx601 and Saline solution in people with Crohn's Disease, run by Tigenix S.A.U. at 52 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 52 sites in Spain, France, Italy, Germany, Israel and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Combine remission of perianal fistulising Crohn's (time frame: 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01541579, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2019.

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