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

• Register: ClinicalTrials.gov
• Last refreshed on: 2 June 2025
• Main ID: NCT04701411
• Date of registration: 06/01/2021
• Prospective Registration: Yes
• Primary sponsor: Takeda
• Public title: A Study of Darvadstrocel for Treating Complex Perianal Fistulas in Children and Teenagers With Crohn's Disease
• Scientific title: 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
• Date of first enrolment: June 30, 2021
• Target sample size: 7
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT04701411
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Israel, Japan, Netherlands, Poland, Spain

Contacts

• Name: Medical Director
• Affiliation: Takeda

Key inclusion & exclusion criteria

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.


Age minimum: 4 Years
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Crohn's Disease

Complex Perianal Fistula

Intervention(s)

Biological: Darvadstrocel

Primary Outcome(s)

Percentage of Participants who Achieve Combined Remission [Time Frame: Week 24]

Secondary Outcome(s)

Percentage of Participants who Achieve Clinical Remission [Time Frame: Up to Week 52]

Percentage of Participants with At Least One Adverse Event (AE) [Time Frame: Up to Week 52]

Percentage of Participants with Potentially Clinically Significant Vital Sign Values [Time Frame: Up to Week 52]

Time to Clinical Remission [Time Frame: Up to Week 52]

Percentage of Participants with At Least One Adverse Event of Special Interest (AESI) [Time Frame: Up to Week 52]

Percentage of Participants with At Least One Serious Adverse Event (SAE) [Time Frame: Up to Week 52]

Time to Clinical Response [Time Frame: Up to Week 52]

Percentage of Participants with Relapse in Participants with Combined Remission at Week 24 [Time Frame: Up to Week 52]

Percentage of Participants with Potentially Clinically Significant Laboratory Values [Time Frame: Up to Week 52]

Percentage of Participants who Achieve Clinical Response [Time Frame: Up to Week 52]

Secondary ID(s)

2020-003193-48

Darvadstrocel-3004

2023-503973-39

EMEA-001561-PIP01-13-M02

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Takeda Development Center Americas, Inc.