A Study of Darvadstrocel for Treating Complex Perianal Fistulas in Children and Teenagers With Crohn's Disease

A Phase 3, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Darvadstrocel in the Treatment of Complex Perianal Fistula in Pediatric Subjects With Crohn's Disease Over a Period of 24 Weeks and an Extended Follow-up Period for a Total of up to 52 Weeks

A perianal fistula is an abnormal passageway that develops between the rectum and the skin near the anus. The fistula is considered complex if it branches into several openings or an abscess is also present.

The main aim of this study is to learn if complex perianal fistulas in children and teenagers close after treatment with darvadstrocel.

2 to 3 weeks before treatment with darvadstrocel, each participant will have surgery to clean the fistula and to drain any abscesses. On the day of treatment, each participant will have the fistula cleaned and will receive an injection of darvadstrocel near the fistula, under anesthetic.

For up to 1 year after treatment, participants will regularly visit the clinic for follow-up. The fistula will be examined and any side effects from the treatment will be recorded. Participants will have an MRI at one clinic visit (about 24 weeks after treatment).

Study Overview

• Status: Terminated
• Conditions: Crohn's Disease; Complex Perianal Fistula
• Intervention / Treatment: Biological: Darvadstrocel

Detailed Description

The drug being tested in this study is called darvadstrocel (Cx601, cell suspension containing 120 million cells of allogeneic expanded adipose-derived mesenchymal stem cells [eASCs]). Darvadstrocel is being tested to treat complex perianal fistula in pediatric participants who have Crohn's disease (CD). This study will look at the safety and efficacy of darvadstrocel in the treatment of complex perianal fistula in CD.

The study will enroll at least 20 patients who will receive a single dose of darvadstrocel.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 52 weeks.

Participants will make multiple visits to the clinic. In unavoidable circumstances, such as the coronavirus disease 2019 pandemic, exceptions may be granted for alternative methods for conducting participant visits with approval by the medical monitor and/or sponsor.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Be’er Ya‘aqov, Israel, 7033001
    • Shamir Medical Center (Assaf Harofeh)
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 9124001
    • Hadassah University Hospital-Mt. Scopus
  • Petah Tikva, Israel, 4920235
    • Schneider Children's Medical Center
• Japan
  • Bunkyō City, Japan, 113-8431
    • Juntendo University Hospital
  • Bunkyō City, Japan, 113-8519
    • Medical Hospital, Tokyo Medical and Dental University
  • Sendai, Japan, 989-3126
    • Miyagi Children's Hospital
  • Shimotsuke-shi, Japan, 329-0498
    • Jichi Medical University Hospital
  • Tsu, Japan, 514-8507
    • Mie University Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC, locatie AMC
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen (UMCG)
  • Rotterdam, Netherlands, 3000 CA
    • Erasmus Medisch Centrum
• Poland
  • Krakow, Poland, 30-663
    • Uniwersytecki Szpital Dzieciecy w Krakowie
  • Rzeszów, Poland, 35-302
    • Gabinet Lekarski Bartosz Korczowski
  • Warsaw, Poland, 04-730
    • Instytut "Pomnik - Centrum Zdrowia Dziecka"
• Spain
  • Badalona, Spain, 8916
    • Hospital Universitari Germans Trias i Pujol
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 8950
    • Hospital Sant Joan de Déu
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Nino Jesus
  • Málaga, Spain, 29011
    • Hospital Materno-Infantil de Malaga

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 13 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Has a CD diagnosis based on accepted clinical, endoscopic, histological and/or radiologic criteria at least 6 months before the screening visit.
2. Has complex perianal fistula refractory to at least one of the following treatments: immunosuppressants or biologics (anti-TNFs, anti-integrin, anti-interleukin [IL] 12/23). Fistula(s) refractory to therapy is defined in this study as follows: Immunosuppressants: Inadequate response after 3 months, based on clinical assessment, or more treatment with azathioprine, 6-mercaptopurine or methotrexate. Biologics: Inadequate response after 14 weeks (16 weeks for anti-IL 12/23), based on clinical assessment, or more standard treatment for induction and maintenance.

3. A complex perianal fistula(s) that meets one or more of the following criteria, modified from the American Gastroenterological Association (AGA) technical review: High intersphincteric, transsphincteric, extrasphincteric, or suprasphincteric as assessed by MRI. Presence of 2 or 3 external openings (tracts) as assessed by clinical examination. Associated fluid (abscess) collections as determined by MRI.

   This study requires that the participant has complex perianal fistulas with a maximum of 2 internal openings and a maximum of 3 external openings, based on clinical assessment. Darvadstrocel treatment is targeted for fistulas that connect between internal and external openings. A central reading of a locally performed pelvic MRI will be performed to confirm the location of the fistula and potential associated perianal abscess(es). Fistulas must have been draining for at least 6 weeks before the screening visit. Participants with actively draining simple subcutaneous fistulas, at the time of the screening visit, are not allowed in this study.

4. Has inactive or mildly active luminal CD defined by meeting all of the following criteria:

   1. Colonoscopy, flexible sigmoidoscopy or rectoscopy performed either at screening or within the 6 months before screening, demonstrating no rectal ulcers larger than 0.5 cm. A participant who has documented rectal ulcers larger than 0.5 cm within the 6 months before screening but has undergone subsequent treatment may be eligible if there are no rectal ulcers larger than 0.5 cm on a sigmoidoscopy or rectoscopy performed after treatment or at the time of screening.
   2. The improvement of, or no worsening in stool frequency, sustained for 1 week or more, in the interval between the colonoscopy, flexible sigmoidoscopy or rectoscopy in inclusion criteria 4(a) and the screening visit.
   3. No initiation or intensification of treatment with corticosteroids, immunosuppressants, or monoclonal antibody dose regimen between the colonoscopy, flexible sigmoidoscopy or rectoscopy in inclusion criteria 4(a) and the screening visit.

Exclusion Criteria:

1. Has received any investigational compound within 12 weeks/84 days before screening.
2. Has received darvadstrocel/eASC in a previous clinical study or as a therapeutic agent.
3. The participant weighs <10 kg at screening.
4. Has concomitant perianal fistula(s) with only internal or external opening(s).
5. Has concomitant internal fistula(s) such as ileo-vesical, rectovaginal or ileo-colonic fistula(s).
6. Has an abscess >2 cm, unless resolved in the preparation procedure.
7. Has rectal and/or anal stenosis, and/or active proctitis, which would restrict the surgical procedure.
8. The participant underwent surgery for the fistula other than drainage or seton placement.
9. Has diverting stomas.
10. Has ongoing systemic corticosteroid treatment or has been treated with systemic corticosteroids within 4 weeks before screening.
11. The participant requires new treatment with immunosuppressants/anti-TNF agents during the screening period.
12. 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. 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.
13. The participant requires surgery in the perianal region for reasons other than fistulas at the time of screening or foreseen either during the study and/or during the 24 weeks after treatment administration.
14. Has malignant tumor or a prior history of any malignant tumor, including any type of fistula carcinoma.
15. Has current or recent (within 3 months before the screening) history of abnormal, severe, progressive, uncontrolled hepatic, hematologic, gastrointestinal (except CD), endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral disease.
16. Has either congenital or acquired immunodeficiencies, including participants known to be HIV carriers or participants with, in the judgment of the investigator, are suspected to have monogenic inflammatory bowel disease.
17. Has previously received a bone marrow transplant.
18. Has a contraindication to MRI scan or other planned study procedures.
19. Has a contraindication to the anesthetic procedure.
20. Had major surgery or severe trauma within 6 months before the screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darvadstrocel; Participants were administered darvadstrocel (Cx601), 24 milliliters (mL) suspension of 120 million cells as a perilesional injection, once on Day 0.	Biological: Darvadstrocel; Darvadstrocel perilesional injection.; Other Names: Cx601

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Combined Remission	Combined remission was defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression, and absence of abscess(es) >2 centimeters (cm) (in at least 2 dimensions) of the treated perianal fistula(s) confirmed by central magnetic resonance imaging (MRI) assessment.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Clinical Remission	Clinical remission was defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression.	Weeks 24 and 52
Percentage of Participants Who Achieved Clinical Response	Clinical response was defined as closure of at least 50% of all treated external openings that were draining at baseline despite gentle finger compression.	Weeks 24 and 52
Time to Clinical Remission	Time to Clinical Remission was defined as the time in weeks from treatment start to first visit at which clinical remission was observed before Week 52; where clinical remission is said to have occurred if a clinical assessment showed closure of all treated external openings that were draining at baseline despite gentle finger compression. Participants without documented time to clinical remission by the end of study (Week 52), were censored at the date of last assessment along with the participants who discontinued without clinical remission before Week 52 at the date of last visit.	Up to Week 52
Time to Clinical Response	Time to clinical response defined as the time in weeks from treatment start to first visit at which clinical response was observed before Week 52; where clinical response is said to have occurred if a clinical assessment showed closure of at least 50% of all treated external openings that were draining at baseline despite gentle finger compression. Participants without documented time to clinical response by the end of study (Week 52), were censored at the date of last assessment along with the participants who discontinued without clinical response before Week 52 at the date of last visit.	Up to Week 52
Percentage of Participants With Relapse in Participants With Combined Remission at Week 24	Relapse was defined as reopening of any of the treated fistula(s) external openings with active drainage as clinically assessed in participants who were in combined remission at Week 24.	From Week 24 to Week 52
Percentage of Participants With At Least One Treatment-Emergent Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE is an AE which occurs after exposure to study treatment.	Up to Week 52
Percentage of Participants With At Least One Treatment-Emergent Serious Adverse Event (SAE)	An 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.	Up to Week 52
Percentage of Participants With At Least One Treatment-Emergent Adverse Event of Special Interest (AESI)	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.	Up to Week 52
Percentage of Participants With Potentially Clinically Significant Vital Sign Values	Vital signs include body temperature (oral measurement), blood pressure (systolic and diastolic, resting more than 5 minutes), and heart rate (beats per minute).	Up to Week 52
Percentage of Participants With Potentially Clinically Significant Laboratory Values	Laboratory parameters include hematology, biochemistry, and urinalysis.	Up to Week 52

Collaborators and Investigators

• Sponsor: Takeda
• Collaborators: Takeda Development Center Americas, Inc.
• Investigators: Study Director: Medical Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Actual): May 7, 2025
• Study Completion (Actual): May 7, 2025

Study Registration Dates

• First Submitted: January 6, 2021
• First Submitted That Met QC Criteria: January 7, 2021
• First Posted (Actual): January 8, 2021

Study Record Updates

• Last Update Posted (Estimated): November 13, 2025
• Last Update Submitted That Met QC Criteria: November 6, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Drug therapy.
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: Darvadstrocel-3004; 2020-003193-48 (EudraCT Number); EMEA-001561-PIP01-13-M02 (Other Identifier: EU PIP number); 2023-503973-39-00 (Ctis: EU CTIS Number); jRCT2033200314 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be reidentified (due to the limited number of study participants/study sites.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No