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

NCT04118088 | Terminated Phase 4 Results FDA Drug

• 4 other identifiers: Alofisel-4001EUPAS314392022-503014-23-002017-002491-10
• Study Type: interventional
• Target: 53
• Locations: 6 countries
• Sites: 30

Brief 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. A magnetic resonance imaging (MRI) will be performed several times during the study.

Conditions

Crohn's Disease; Complex Perianal Fistula

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (4)

• 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.

  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

• 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.

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

• 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.

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

• 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.

  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)

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

  At Weeks 24 and 156 post-repeat darvadstrocel administration

• Percentage of Participants Who Achieved Clinical Remission

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

• Percentage of Participants Who Achieved Clinical Response

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

• Percentage of Participants With Relapse From Week 24 Combined Remission

  From Week 24 to Week 156 post-repeat darvadstrocel administration

• Time to Relapse

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

Study Arms (1)

Darvadstrocel

EXPERIMENTAL

Participants 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.

Biological: Darvadstrocel

Interventions

Darvadstrocel BIOLOGICAL

Darvadstrocel suspension of human expanded adipose stem cells.

Also known as: Alofisel, Cx601

Darvadstrocel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• a) 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.

Sponsors & Collaborators

• Takeda: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (30)

Akh Wien

Vienna, 1090, Austria

Location

NH Hospital a.s.

Hořovice, 268 31, Czechia

Location

ISCARE a.s.

Prague, 190 00, Czechia

Location

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

Nice, Alpes-Maritimes, 6202, France

Location

CHRU Hopital de Pontchaillou - Maladies De L'Appareil Digesti

Rennes, Ille-et-Vilaine, 35033, France

Location

CHRU de Lille - Hopital Claude Huriez - Gastroenterologie

Lille, Nord, 59037, France

Location

CHU AMIENS PICARDIE Site SUD Hepato-Gastroenterology

Amiens, Picardie, 80054, France

Location

Centre Hospitalier Lyon Sud - Gastroenterology

Pierre-Bénite, Rhone, 69495, France

Location

Paris St. Joseph Hospital

Paris, 75014, France

Location

Groupe Hospitalier Diaconesses Croix Saint Simon

Paris, 75020, France

Location

Klinikum Dresden, University Hospital Dresden

Dresden, Saxony, 1307, Germany

Location

Stadtisches Klinikum Luneburg

Luneburg, Schleswig-Holstein, 21339, Germany

Location

Charite - Campus Benjamin Franklin

Berlin, 12200, Germany

Location

Krankenhaus Waldfriede

Berlin, 14163, Germany

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem

Jerusalem, 91120, Israel

Location

Rabin Medical Center, Beilinson Hospital

Petah Tikva, 49100, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Chaim sheba Medical Center

Tel Litwinsky, 5262000, Israel

Location

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Hospital Universitario Nuestra Senora de la Candelaria

Santa Cruz de Tenerife, Canary Islands, 38010, Spain

Location

H. Donostia

Donostia / San Sebastian, San Sebastian, 20014, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 8036, Spain

Location

Hospital Universitari de Bellvitge

Barcelona, 8907, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

C.H.U. de Pontevedra

Pontevedra, 36071, Spain

Location

H.C.U. de Valencia

Valencia, 46010, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Related Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Limitations and Caveats

The study was terminated early based on sponsor's decision.

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2019
• First Posted: October 8, 2019
• Study Start: December 22, 2020
• Primary Completion: February 14, 2025
• Study Completion: February 14, 2025
• Last Updated: January 22, 2026
• Results First Posted: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

FR (7); AU (1); IL (5); DE (4); CZ (2); ES (11)