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Crohn's DiseasePhase 4EMPIRENCT04118088

A Study of Darvadstrocel in Adults With Crohn's Disease and Complex Perianal Fistula

A Phase 4 study testing Darvadstrocel in people with Crohn's Disease and Complex Perianal Fistula, run by Takeda at 30 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The main aim is to check the long term side effects of a repeat treatment of darvadstrocel and to see if that treatment improves symptoms of Crohn's disease and complex perianal fistula. Participants will attend 8 clinic visits and will receive 1 treatment of darvadstrocel at the third visit. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Crohn's Disease, Complex Perianal Fistula
What is being tested?
Darvadstrocel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
30 sitesin 6 countries
Study dates
22 Dec 2020to 14 Feb 2025
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
  • The participant signs and dates a written, ICF and any required privacy authorization before the initiation of any study procedures.
  • The participant is male or female and aged 18 years or older.
  • The participant has complex perianal fistula(s) with a maximum of 2 internal openings and a maximum of 3 external openings based on clinical assessment and a reading of a locally-performed contrast enhanced (gadolinium) pelvic MRI. Fistula(s) must have been draining for at least 6 weeks prior to baseline visit. A complex perianal fistula is defined as a fistula that meets 1 or more of the following criteria:
  • High inter-sphincteric, high trans-sphincteric, extra-sphincteric or suprasphincteric.
  • Presence of ≥2 external openings.
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  • 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.
  • The participant has already received treatment with darvadstrocel for a complex perianal fistula at least 6 months prior to baseline visit for retreatment, and their physician has planned a repeat treatment administration for the original tract (full remission not obtained or relapse of fistula draining) or for a new complex perianal fistula tract.
  • The participant has controlled or mildly active Crohn's disease (CD) (defined as patient reported outcomes measure derived from CDAI patient reported outcome score-2 [PRO-2] score <14).
  • A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use barrier method of contraception (e.g. condom with or without spermicide) from signing of informed consent and until 1 year after repeat administration.
  • A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use a highly effective/effective method of contraception from signing of informed consent and until 1 year after repeat administration.

Who cannot join

  • The participant has lack of clinical response to prior treatment with darvadstrocel, where clinical response is defined as closure of at least 50% of all treated external fistula openings that were draining at baseline despite gentle finger compression or in the case of a unique fistula, a partial closure of the fistula.
  • The participant has a history of hypersensitivity or allergies to darvadstrocel or related compounds.
  • The participant has a history of hypersensitivity or allergies to penicillin or to aminoglycosides; Dulbecco modified eagle medium; bovine serum; local anesthetics or gadolinium.
  • The participant is currently participating in a double-blind clinical study with darvadstrocel. Participants participating in the ongoing INSPIRE registry (Alofisel-5003) study would need to withdraw from that study in order to enroll in this study.
  • The participant is currently receiving or has received any other investigational medicinal product (IMP) within the last 3 months or at least 5 times the respective elimination half-life time, whichever is longer, before signing the ICF.
  • The participant has known or suspected COVID-19 by the investigator within the past 2 months (additional testing may be performed at the discretion of the investigator). Positive antibody testing for COVID without other evidence of current or recent active infection does not exclude participation.
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  • Participants who were in screening at the time that COVID 19-related factors resulted in discontinuation may also be rescreened with approval of the sponsor or designee.
  • The participant has major alterations in any of the following laboratory tests:
  • Serum creatinine levels >1.5 times the upper limit of normal (ULN).
  • Total bilirubin >1.5 × ULN.
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3.0 × ULN.
  • Hemoglobin <10.0 grams per deciliter (g/dL).
  • Platelets <75.0 × 10^9 per liter (/L).
  • Albumin <3.0 g/dL.
  • The participant has an increased risk for a surgical procedure.
  • The participant has a known chronically active hepatopathy of any origin, including cirrhosis and participants with persistent positive hepatitis B surface antigen and quantitative hepatitis B virus polymerase chain reaction (PCR) or positive serology for hepatitis C virus (HCV) and quantitative HCV PCR within 6 months before the baseline visit.
  • If female, the participant is pregnant or breastfeeding, or intending to become pregnant before participating in this study, during the study, or intending to donate ova during such time period.
  • If male, the participant intends to donate sperm during this study.
  • The participant has a contraindication to MRI scan (e.g., due to the presence of pacemaker, hip replacement, severe claustrophobia, or renal insufficiency as defined by local clinical guidelines).
  • The participant has a contraindication to the anesthetic procedure.
  • The participant has severe rectal and/or anal stenosis that would make it impossible to follow the surgery procedure.
  • The participant has severe proctitis (rectal ulcers >0.5 cm) that would make it impossible to follow the surgery procedure.
  • The participant has any prior invasive malignancy diagnosed within the last 3 years before baseline visit. Participants with basal cell carcinoma of the skin completely resected outside the perineal region can be included.
  • The participant has a current or recent (within 6 months before the baseline visit) history of severe, progressive, and/or uncontrolled hepatic, hematologic, gastrointestinal (other than CD), renal, endocrine, pulmonary, cardiac, neurologic, or psychiatric disease that may result in participant's increased risk from study participation and/or lack of compliance with study procedures.
  • The participant has had major surgery of the gastrointestinal tract within 6 months before baseline or any minor surgery of the gastrointestinal tract 3 months before baseline.
  • The participant had local major perianal surgery, and/or treatment with darvadstrocel within 6 months before baseline. The abscess drainage, cleaning surgery, or seton placement are not considered as "local major surgery" in this protocol.
  • The participant does not wish to or cannot comply with study procedures.

Trial locations and contacts

30 sites in 6 countries.

30 sites in 6 countries

Spain11 sites

  • Hospital Universitario Vall d'Hebron

    Barcelona, 8035

  • Hospital Clinic de Barcelona

    Barcelona, 8036

  • Hospital Universitari de Bellvitge

    Barcelona, 8907

  • H. Donostia

    Donostia / San Sebastian, San Sebastian, 20014

  • Hospital Universitario Fundacion Jimenez Diaz

    Madrid, 28040

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario Son Espases

    Palma de Mallorca, Balearic Islands, 07120

  • C.H.U. de Pontevedra

    Pontevedra, 36071

  • Hospital Universitario Nuestra Senora de la Candelaria

    Santa Cruz de Tenerife, Canary Islands, 38010

  • H.C.U. de Valencia

    Valencia, 46010

  • Hospital Universitari i Politecnic La Fe

    Valencia, 46026

Other trials in Spain

France7 sites

  • CHU AMIENS PICARDIE Site SUD Hepato-Gastroenterology

    Amiens, Picardie, 80054

  • CHRU de Lille - Hopital Claude Huriez - Gastroenterologie

    Lille, Nord, 59037

  • CHU de Nice - Hopital de l'Archet II - Gastro-Enterologie, Hepatologi

    Nice, Alpes-Maritimes, 6202

  • Paris St. Joseph Hospital

    Paris, 75014

  • Groupe Hospitalier Diaconesses Croix Saint Simon

    Paris, 75020

  • Centre Hospitalier Lyon Sud - Gastroenterology

    Pierre-Bénite, Rhone, 69495

  • CHRU Hopital de Pontchaillou - Maladies De L'Appareil Digesti

    Rennes, Ille-et-Vilaine, 35033

Other trials in France

Israel5 sites

  • Shaare Zedek Medical Center

    Jerusalem, 9103102

  • Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem

    Jerusalem, 91120

  • Rabin Medical Center, Beilinson Hospital

    Petah Tikva, 49100

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 64239

  • Chaim sheba Medical Center

    Tel HaShomer, 5262000

Other trials in Israel

Germany4 sites

  • Charite - Campus Benjamin Franklin

    Berlin, 12200

  • Krankenhaus Waldfriede

    Berlin, 14163

  • Klinikum Dresden, University Hospital Dresden

    Dresden, Saxony, 1307

  • Stadtisches Klinikum Luneburg

    Luneburg, Schleswig-Holstein, 21339

Other trials in Germany

Czechia2 sites

  • NH Hospital a.s.

    Hořovice, 268 31

  • ISCARE a.s.

    Prague, 190 00

Other trials in Czechia

Austria1 site

  • Akh Wien

    Vienna, 1090

Other trials in Austria

About this study

Official title: Postauthorization Safety Study of the Long-Term Safety and Efficacy of Repeat Administration of Darvadstrocel in Patients With Crohn's Disease and Complex Perianal Fistula

The main aim is to check the long term side effects of a repeat treatment of darvadstrocel and to see if that treatment improves symptoms of Crohn's disease and complex perianal fistula. Participants will attend 8 clinic visits and will receive 1 treatment of darvadstrocel at the third visit. A magnetic resonance imaging (MRI) will be performed several times during the study.

Read the detailed description

The biological being tested in this study is called darvadstrocel (Alofisel). This study is examining the long-term safety and efficacy of a repeat dose of darvadstrocel in people who have Crohn's disease and complex perianal fistula.

The study will enroll approximately 50 patients. Participants will be assigned to one treatment group to receive:

  • Darvadstrocel 120 million cells

All participants would be allowed to receive one repeat dose of darvadstrocel in the whole study. This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 3 years. Participants will make multiple visits to the clinic.

Being tested
Darvadstrocel
Keywords
Drug therapy
Medical subject headings
Crohn Disease

What participants receive

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

  • DarvadstrocelBiological

    Also called Alofisel, Cx601

    Darvadstrocel suspension of human expanded adipose stem cells.

Study groups in NCT04118088
Study groupRoleWhat they receive
DarvadstrocelExperimentalParticipants who had previously received darvadstrocel were administered a single repeat dose of darvadstrocel, 24 mililiter (mL) suspension of 120 million cells (5 million cells/mL), as a perilesional injection into the fistula.
Receives: Biological: Darvadstrocel

What is being measured

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

  1. Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)

    An adverse event (AE) is any untoward medical occurrence in a participant administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an AE with an onset that occurs after receiving study drug.

    Measured: From signing of informed consent form (ICF) up to 156 weeks post-repeat administration (the only administration in this study), up to approximately 164 weeks

  2. Percentage of Participants With at Least One Treatment Emergent Serious Adverse Event (TESAE)

    A serious adverse event (SAE) is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent SAE is an SAE which occurs after exposure to study treatment. Percentages were rounded off to the nearest single decimal place.

    Measured: From signing of ICF up to 156 weeks post-repeat administration (the only administration in this study), up to approximately 164 weeks

  3. Number of Reported Pregnancies During Study

    Female participants and/or female partners of male participants who become pregnant following treatment with the study product and reported the pregnancy on a paper pregnancy report form immediately or within 24 hours of awareness were reported.

    Measured: From administration of repeat dose up to 156 weeks post-repeat administration

  4. Percentage of Participants With Treatment Emergent Adverse Event of Special Interest (TEAESI)

    Adverse event of special interests (AESIs) include immunogenicity/alloimmune reactions, hypersensitivity reactions, ectopic tissue formation, medication errors, tumorigenicity, and transmission of infectious agents. A treatment-emergent AESI is an AESI which occurs after exposure to study treatment.

    Measured: From signing of ICF up to 156 weeks post-repeat administration (the only administration in this study), up to approximately 164 weeks

Secondary outcomes (7)

  1. Percentage of Participants Who Achieved Combined Remission of Perianal Fistula(s)

    Combined remission was defined as the closure of all treated external openings that were draining at baseline, despite gentle finger compression and absence of collection(s) >2 centimeters (cm) (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by central magnetic resonance imaging (MRI) assessment.

    Measured: At Weeks 24 and 156 post-repeat darvadstrocel administration

  2. Percentage of Participants Who Achieved Clinical Remission

    Clinical remission was defined as closure of all treated external fistula openings that were draining at baseline despite gentle finger compression.

    Measured: At Weeks 6, 24, 52, 104, and 156 post-repeat darvadstrocel administration

  3. Percentage of Participants Who Achieved Clinical Response

    Clinical response was defined as closure of at least 50% of all treated external fistula openings that were draining at baseline despite gentle finger compression.

    Measured: At Weeks 6, 24, 52, 104, and 156 post-repeat darvadstrocel administration

  4. Percentage of Participants With Relapse From Week 24 Combined Remission

    Relapse was defined as reopening of any of the treated fistula(s) external openings with active drainage as clinically assessed that were in the combined remission at Week 24 or the development of a collection >2 cm (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by centrally read MRI assessment.

    Measured: From Week 24 to Week 156 post-repeat darvadstrocel administration

  5. Time to Relapse

    Time to Relapse was defined as the time in days to reopening of any of the treated fistula(s) external openings with active drainage as clinically assessed, relative to Week 24.

    Measured: From Week 24 to the day of relapse post-repeat darvadstrocel administration

  6. Percentage of Participants With New Perianal Abscess in Treated Fistula

    Measured: At Weeks 6, 24, 52, 104, and 156 post-repeat darvadstrocel administration

  7. Change From Baseline in Score of Discharge and Pain Items of Perianal Disease Activity Index (PDAI) Score

    The PDAI is a scoring system to evaluate the severity of perianal lesion associated with Crohn's disease. It includes the following 5 items: (a) discharge; (b) pain; (c) restriction of sexual activity; (d) type of perianal disease; and (e) degree of induration. Each item is graded on a 5-point scale ranging from no symptoms (score of 0) to severe symptoms (score of 4). Higher score means more severe disease.

    Measured: Baseline to Weeks 6, 24, 52, 104, and 156 post-repeat darvadstrocel administration

Timeline

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

  1. First posted8 Oct 2019
  2. Study start22 Dec 2020
  3. Primary completion14 Feb 2025
  4. Study completion14 Feb 2025

Why it stopped: Sponsor decision

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 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04118088
Sponsor's protocol ID
Alofisel-4001
Other IDs
EUPAS31439, 2022-503014-23-00, 2017-002491-10, 2017
Acronym
EMPIRE
Status last verified
Jan 2026
First submitted
4 Oct 2019
Last updated
22 Jan 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Darvadstrocel in people with Crohn's Disease and Complex Perianal Fistula, run by Takeda at 30 sites in 6 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 11 inclusion and 27 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: stopped early, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in Spain, France, Israel, Germany, Czechia and 1 more country. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) (time frame: From signing of informed consent form (ICF) up to 156 weeks post-repeat administration (the only administration in this study), up to approximately 164 weeks). The study lists 4 primary outcomes in all. 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 NCT04118088.

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 22 Jan 2026.

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