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CompletedNCT03706456Updated Jun 10, 2024Results posted

Phase 3 Study of Cx601 in Participants With Complex Perianal Fistulising Crohn's Disease

A Phase 3 interventional study of Darvadstrocel in Complex Perianal Fistulas in Adult Participants With Crohn's Disease, sponsored by Takeda. Completed at 11 sites in Japan. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-10.

Sponsored by Takeda · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
22
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to evaluate the efficacy of darvadstrocel for the treatment of complex perianal fistulas in adult participants with Crohn's disease over 24 weeks.

Read the detailed description

The drug being tested in this study is called Darvadstrocel (Cx601). This study will assess the efficacy for 24 and 52 weeks, and safety for 156 weeks of darvadstrocel when administered with intralesional injection in adult participants with Crohn's disease whose complex perianal fistulas were previously treated and refractory.

The study enrolled 22 participants. All participants who will meet the criteria will be assigned to screening period for approximately 5 weeks and after that will be enrolled the treatment period which will be the day of study product administration. After the treatment period, this study will include the follow-up period for approximately 52 weeks after study product administration, and the long-term follow-up period from Week 52 to Week 156.

This multi-center trial will be conducted in Japan. The overall time to participate is totally approximately 156 weeks (3 years) from the start of treatment period plus follow-up and long-term follow-up period. Participants will make multiple visits to the clinic and a final visit 156 weeks after treatment of study product for a follow-up assessment.

02

Conditions studied

  • Complex Perianal Fistulas in Adult Participants With Crohn's Disease
03

In context

Lead sponsor

Takeda is the lead sponsor of 1,025 studies on the registry; 91 are open to participants now.

Of its 177 completed or terminated interventional studies of FDA-regulated products, 153 (86%) have results posted.

Browse Takeda studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. In the opinion of the investigator, the participant is capable of understanding and complying with the protocol requirements.
  2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
  3. The participant who was diagnosed with Crohn's disease at least 6 months prior to the screening period according to the Diagnostic Criteria for Crohn's Disease issued by Research Group for Intractable Inflammatory Bowel Disease Designated as Specified Disease by the Ministry of Health, Labour and Welfare (MHLW) of Japan (revised January 2017).
  4. The participant is either a male or female outpatient, aged 18 years or older at the time of signing the informed consent form.
  5. The participant who has non-active or mildly active Crohn's disease defined by the Crohn's disease activity index (CDAI) =\<220 evaluated at any time between Visit 1 and Visit 2.

  6. The participant who has complex perianal fistulas with a maximum of 2 internal openings and a maximum of 3 external openings, confirmed by clinical assessment and MRI. All of the external openings must connect to internal openings. Fistula must have been draining for at least 6 weeks prior to the screening. Complex perianal fistula is defined as the one that meets 1 or more of the following criteria:

    • High (ie, above the dentate line) inter-sphincteric or trans-sphincteric fistula, extrasphincteric fistula, or supra-sphincteric fistula.
    • Presence of >=2 external openings (tracts).
    • Associated fluid collections.

  7. The participant whose perianal fistulas were previously treated and have shown an inadequate response (absence of closure of part or all fistula tract, or new fistula during induction treatment) or a loss of response (fistula relapse after complete closure of initial fistula, or fistula worsening after partial closure of initial fistula during maintenance treatment) while they were receiving either immunosuppressants or biologics, or having documented intolerance (occurrence, at any time, of an unacceptable level of treatment-related side effects that makes necessary treatment discontinuation) to any of these treatments administered at least approved or recommended doses during the minimum period mentioned;

    • Antibiotics (ciprofloxacin or metronidazole): 1 or more month treatment.
    • Immunosuppressants (azathioprine, 6-mercaptopurine or methotrexate): 3 or more months treatment.
    • Biologics (anti-tumor necrosis factors [TNFs], anti-integrin or anti-interleukin [IL]-12/23): 14 or more weeks (16 or more weeks for anti-IL-12/23) standard treatment for induction or maintenance.
  8. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent up to Week 52 of the study.
  9. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent up to Week 52 of the study.

Exclusion criteria

Exclusion Criteria:

  1. The participant whose CDAI is >220 at any time between Visit 1 and Visit 2, or who has active Crohn's disease requiring a new of escalating immediate therapy.
  2. The participant who has concomitant rectovaginal or rectovesical fistulas.
  3. The participant who has >2 internal openings of >3 external openings.
  4. The participant who is naïve to protocol required treatment for complex perianal fistulising Crohn's disease (ie, antibiotics, immunosuppressants or biologics).
  5. The participant who has an abscess or collections >2 cm.
  6. The participant who has rectal and/or anal stenosis and/or active proctitis, which would restrict the surgical procedure.
  7. The participant who underwent surgery other than drainage or seton placement for the to be treated fistula.
  8. The participant who has diverting stomas.
  9. The participant who was treated with systemic steroids in the 4 weeks prior to study product administration.
  10. The participant receiving cytapheresis therapy.
  11. The participant who requires new treatment with immunosuppressants/biologics/non-tapered systematic steroids during the screening period.
  12. The participant who has renal impairment defined by creatinine clearance below 60 mL/minute calculated using Cockcroft-Gault formula or by serum creatinine >=1.5 × upper limit of normal (ULN).
  13. The participant who has hepatic impairment defined by both total bilirubin >=1.5 × ULN, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >=2.5 × ULN.
  14. The participant who has history of abuse of alcohol or other addictive substances in the 6 months prior to the screening period.
  15. The participant who has malignant tumour or who has a history of malignant tumour, including any type of fistula carcinoma.
  16. The participant who has abnormal, severe, progressive, uncontrolled hepatic, hematological, gastrointestinal (except Crohn's disease), endocrine, pulmonary, cardiac, neurological, psychiatric, or cerebral disease, or the participant who developed any of the above diseases within 3 months prior to the screening period.
  17. The participant who has congenital or acquired immunodeficiency, including participants known to be Human Immunodeficiency Virus (HIV) carriers.
  18. The participant who has clinically significant chronically active hepatopathy of any origin, including hepatic cirrhosis, and participants who is persistent positive for hepatitis B virus (HBV) surface antigen (HBsAg) and quantitative HBV polymerase chain reaction (PCR), or positive serology for hepatitis C virus (HCV) and quantitative HCV-PCR within 6 months prior to the screening period.
  19. The participant who has known allergies or hypersensitivity to antibiotics (including but not limited to penicillin, streptomycin, gentamicin, aminoglycosides), Human Serum Albumin (HSA), bovine-derived materials, local anesthetics or gadolinium (MRI contrast agent).
  20. The participant for whom MRI scan is contraindicated (eg, due to the presence of a pacemaker, a history of hip replacements, or severe claustrophobia).
  21. The participant who has major surgery (eg, surgery under general anesthesia, laparotomy, thoracotomy, craniotomy) or severe trauma within 6 months prior to the screening period.
  22. The female participant who is pregnant, or is lactating.
  23. The participant who has received any investigational drug within 12 weeks (84 days) prior to the screening.
  24. The participant who has received expanded allogeneic adipose-derived stem cells (eASC) in a previous clinical study or as a therapeutic agent.
  25. The participant who needs perianal surgery other than fistulas preparation required by the protocol during the screening, or the participant who will receive a perianal surgery within 24 weeks after study product administration.
  26. The participant for whom anesthesia is contraindicated.
  27. The participant who received excluded medications or treatment.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
22 participants (actual)

Study arms

  • Experimental
    Darvadstrocel 24 mL

    Darvadstrocel (Cx601) 24 mL suspension of 120 million cells of expanded allogeneic adipose-derived stem cells (eASC) as an intralesional injection, once on Day 1.

    Biological: Darvadstrocel

Interventions

  • BiologicalDarvadstrocel

    Darvadstrocel cell suspension for intralesional injection.

    Also known as: Cx601

06

What researchers measure

Primary outcomes

  1. Percentage of Participants With Combined Remission of Perianal Fistulising Crohn's Disease (CD) at Week 24

    Combined remission of perianal fistulising CD is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression, and absence of collections \>2 cm in the treated fistulas, confirmed by central magnetic resonance imaging (MRI) assessment at Week 24 visit. In case of missing values, last observation carried forward (LOCF) method was applied. Percentages are rounded off to the nearest decimal point.

    Time frame: Week 24

Secondary outcomes

  1. Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 24

    Clinical remission of perianal fistulising CD is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression at Week 24 Visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point.

    Time frame: Week 24

  2. Percentage of Participants With Response of Perianal Fistulising CD at Week 24

    Response of perianal fistulising CD is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at Screening despite gentle finger compression at Week 24 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point.

    Time frame: Week 24

  3. Time to Clinical Remission of Perianal Fistulising CD by Week 24

    Time to clinical remission is defined as the time from the study product administration to the first visit by which clinical remission is observed. Clinical remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression.

    Time frame: Up to Week 24

  4. Time to Response of Perianal Fistulising CD by Week 24

    Time to response is defined as the time from the study product administration to the first visit by which response is observed. Response is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at Screening despite gentle finger compression.

    Time frame: Up to Week 24

  5. Percentage of Participants With Relapse of Perianal Fistulising CD at Week 24 in Participants With Clinical Remission at a Previous Visit

    Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection \>2 cm in the treated fistulas confirmed by central MRI assessment in participants who achieved clinical remission before Week 24. LOCF method was applied. Percentages are rounded off to the nearest decimal point.

    Time frame: Week 24

  6. Time to Relapse of Perianal Fistulising CD by Week 24 in Participants With Clinical Remission at a Previous Visit

    Time to Relapse is defined as the time from the first visit by which clinical remission is observed to the first visit by which relapse is observed. Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection \>2 cm in the treated fistulas confirmed by central MRI assessment.

    Time frame: Up to Week 24

  7. Change From Baseline in Perianal Disease Activity Index (PDAI): Total Score at Week 24

    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 where 0 indicates no symptoms and 4 indicates severe symptoms and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

    Time frame: Baseline and Week 24

  8. Change From Baseline in PDAI: Discharge Sub-Score at Week 24

    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. The discharge item is graded on a 5-point scale where 0 indicates no symptoms and 4 indicates severe symptoms and total range of score is from 0 to 4. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

    Time frame: Baseline and Week 24

  9. Change From Baseline in PDAI: Pain Sub-Score at Week 24

    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. The pain item is graded on a 5-point scale where 0 indicates no symptoms and 4 indicates severe symptoms and total range of score is from 0 to 4. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

    Time frame: Baseline and Week 24

  10. Change From Baseline in Crohn's Disease Activity Index (CDAI): Total Score at Week 24

    CDAI score is calculated from the following 8 items: (a) Number of liquid or very soft stools; (b) Abdominal pain; (c) General wellbeing; (d) Extraintestinal complications; (e) Antidiarrhoeal drugs; (f) Abdominal mass; (g) Hematocrit; and (h) Body weight. Scores of some items in CDAI are calculated based on patient diary. Total score ranges from 0 to 600. Higher score means more severe disease and especially severe disease was defined as a value of greater than 450. Negative change from Baseline indicates improvement.

    Time frame: Baseline and Week 24

  11. Change From Baseline in Van Assche Score at Week 24

    The Van Assche score represents the magnetic resonance imaging (MRI)- based severity of perianal lesion associated with Crohn's disease. Based on MRI data, the number, location and extension of fistula tracts, hyperintensity on T2-weighted images, presence or absence of collections (cavities \>3 mm in diameter), and rectal wall involvement will be evaluated. The score range was from 0 to 22. Higher score means more severe disease. Negative change from Baseline indicates improvement.

    Time frame: Baseline and Week 24

  12. Percentage of Participants With Combined Remission of Perianal Fistulising CD at Week 52

    Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at the screening despite gentle finger compression, and absence of collections \>2 cm in the treated fistulas which is confirmed by the central MRI assessment at Week 52 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point.

    Time frame: Week 52

  13. Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 52

    Clinical remission is defined as the clinically confirmed closure of all treated external openings that were draining at screening despite gentle finger compression at Week 52 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point.

    Time frame: Week 52

  14. Percentage of Participants With Response of Perianal Fistulising CD at Week 52

    Response is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at the screening despite gentle finger compression at Week 52 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point.

    Time frame: Week 52

  15. Time to Combined Remission of Perianal Fistulising CD by Week 52

    Time to combined remission is defined as the time from the study product administration to the first visit by which combined remission is observed. Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at the screening despite gentle finger compression, and absence of collections \>2 cm in the treated fistulas which is confirmed by the central MRI assessment.

    Time frame: Up to Week 52

  16. Time to Clinical Remission of Perianal Fistulising CD by Week 52

    Time to clinical remission is defined as the time from the study product administration to the first visit by which clinical remission is observed. Clinical remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression.

    Time frame: Up to Week 52

  17. Time to Response of Perianal Fistulising CD by Week 52

    Time to response is defined as the time from the study product administration to the first visit by which response is observed. Response is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at the Screening despite gentle finger compression.

    Time frame: Up to Week 52

  18. Percentage of Participants With Relapse of Perianal Fistulising CD at Week 52 in Participants With Combined Remission at Week 24

    Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection \>2 cm in the treated fistulas confirmed by central MRI assessment in participants who achieved combined remission at Week 24. Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression, and absence of collections \>2 cm in the treated fistulas, confirmed by the central MRI assessment. LOCF method was applied. Percentages are rounded off to the nearest decimal point.

    Time frame: Week 52

  19. Time to Relapse of Perianal Fistulising CD by Week 52 in Participants With Combined Remission at Week 24

    Time to relapse by Week 52 in participants who achieved combined remission at Week 24 is defined as the time from the combined remission at Week 24 to the first visit by which relapse is observed. Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection \>2 cm in the treated fistulas confirmed by central MRI assessment in participants who achieved combined remission at Week 24. Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression, and absence of collections \>2 cm in the treated fistulas, confirmed by the central MRI assessment.

    Time frame: Up to Week 52

  20. Change From Baseline in PDAI: Total Score at Week 52

    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) and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

    Time frame: Baseline and Week 52

  21. Change From Baseline in PDAI: Discharge Sub-Score at Week 52

    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. The discharge item is graded on a 5-point scale ranging from no symptoms (score of 0) to severe symptoms (score of 4) and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

    Time frame: Baseline and Week 52

  22. Change From Baseline in PDAI: Pain Sub-Score at Week 52

    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. The pain item is graded on a 5-point scale ranging from no symptoms (score of 0) to severe symptoms (score of 4) and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

    Time frame: Baseline and Week 52

  23. Change From Baseline in CDAI: Total Score at Week 52

    CDAI score is calculated from the following 8 items: (a) Number of liquid or very soft stools; (b) Abdominal pain; (c) General wellbeing; (d) Extraintestinal complications; (e) Antidiarrhoeal drugs; (f) Abdominal mass; (g) Hematocrit; and (h) Body weight. Scores of some items in CDAI are calculated based on patient diary. Total score ranges from 0 to 600. Higher score indicates more severe disease and especially severe disease was defined as a value of greater than 450. Negative change from Baseline indicates improvement.

    Time frame: Baseline and Week 52

  24. Change From Baseline in Van Assche Total Score at Week 52

    The Van Assche score represents the MRI-based severity of perianal lesion associated with Crohn's disease. Based on MRI data, the number, location and extension of fistula tracts, hyperintensity on T2-weighted images, presence or absence of collections (cavities \>3 mm in diameter), and rectal wall involvement will be evaluated. The total score ranges from 0 to 22. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

    Time frame: Baseline and Week 52

07

Results

Posted Oct 7, 2021

Participant flow

Participants took part in the study at 9 investigative sites in Japan from 06 March 2019 to 10 February 2023.

Participant flow — Overall Study
MilestoneDarvadstrocel 24 mL
Started22
Completed19
Not completed3
Withdrew: Adverse event1
Withdrew: Lack of efficacy2

Outcome measures

PrimaryPercentage of Participants With Combined Remission of Perianal Fistulising Crohn's Disease (CD) at Week 24

Combined remission of perianal fistulising CD is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression, and absence of collections \>2 cm in the treated fistulas, confirmed by central magnetic resonance imaging (MRI) assessment at Week 24 visit. In case of missing values, last observation carried forward (LOCF) method was applied. Percentages are rounded off to the nearest decimal point.

Time frame:
Week 24
Reported as:
Number · percentage of participants
Percentage of Participants With Combined Remission of Perianal Fistulising Crohn's Disease (CD) at Week 24
percentage of participantsDarvadstrocel 24 mL
Percentage of Participants With Combined Remission of Perianal Fistulising Crohn's Disease (CD) at Week 2459.1 (38.5 to 79.6)
SecondaryPercentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 24

Clinical remission of perianal fistulising CD is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression at Week 24 Visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point.

Time frame:
Week 24
Reported as:
Number · percentage of participants
Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 24
percentage of participantsDarvadstrocel 24 mL
Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 2459.1 (38.5 to 79.6)
SecondaryPercentage of Participants With Response of Perianal Fistulising CD at Week 24

Response of perianal fistulising CD is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at Screening despite gentle finger compression at Week 24 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point.

Time frame:
Week 24
Reported as:
Number · percentage of participants
Percentage of Participants With Response of Perianal Fistulising CD at Week 24
percentage of participantsDarvadstrocel 24 mL
Percentage of Participants With Response of Perianal Fistulising CD at Week 2481.8 (65.7 to 97.9)
SecondaryTime to Clinical Remission of Perianal Fistulising CD by Week 24

Time to clinical remission is defined as the time from the study product administration to the first visit by which clinical remission is observed. Clinical remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression.

Time frame:
Up to Week 24
Reported as:
Median · days
Time to Clinical Remission of Perianal Fistulising CD by Week 24
daysDarvadstrocel 24 mL
Time to Clinical Remission of Perianal Fistulising CD by Week 2430.0 (14.0 to 116.0)
SecondaryTime to Response of Perianal Fistulising CD by Week 24

Time to response is defined as the time from the study product administration to the first visit by which response is observed. Response is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at Screening despite gentle finger compression.

Time frame:
Up to Week 24
Reported as:
Median · days
Time to Response of Perianal Fistulising CD by Week 24
daysDarvadstrocel 24 mL
Time to Response of Perianal Fistulising CD by Week 2418.0 (12.0 to 30.0)
SecondaryPercentage of Participants With Relapse of Perianal Fistulising CD at Week 24 in Participants With Clinical Remission at a Previous Visit

Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection \>2 cm in the treated fistulas confirmed by central MRI assessment in participants who achieved clinical remission before Week 24. LOCF method was applied. Percentages are rounded off to the nearest decimal point.

Time frame:
Week 24
Reported as:
Number · percentage of participants
Percentage of Participants With Relapse of Perianal Fistulising CD at Week 24 in Participants With Clinical Remission at a Previous Visit
percentage of participantsDarvadstrocel 24 mL
Percentage of Participants With Relapse of Perianal Fistulising CD at Week 24 in Participants With Clinical Remission at a Previous Visit25.0 (3.8 to 46.2)
SecondaryTime to Relapse of Perianal Fistulising CD by Week 24 in Participants With Clinical Remission at a Previous Visit

Time to Relapse is defined as the time from the first visit by which clinical remission is observed to the first visit by which relapse is observed. Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection \>2 cm in the treated fistulas confirmed by central MRI assessment.

Time frame:
Up to Week 24
Reported as:
Median · days
Time to Relapse of Perianal Fistulising CD by Week 24 in Participants With Clinical Remission at a Previous Visit
daysDarvadstrocel 24 mL
Time to Relapse of Perianal Fistulising CD by Week 24 in Participants With Clinical Remission at a Previous VisitNA (85.0 to NA)
SecondaryChange From Baseline in Perianal Disease Activity Index (PDAI): Total Score at Week 24

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 where 0 indicates no symptoms and 4 indicates severe symptoms and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

Time frame:
Baseline and Week 24
Reported as:
Mean · score on a scale
Change From Baseline in Perianal Disease Activity Index (PDAI): Total Score at Week 24
score on a scaleDarvadstrocel 24 mL
Baseline4.8 ± 2.15
Change from Baseline at Week 24-2.4 ± 2.22
SecondaryChange From Baseline in PDAI: Discharge Sub-Score at Week 24

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. The discharge item is graded on a 5-point scale where 0 indicates no symptoms and 4 indicates severe symptoms and total range of score is from 0 to 4. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

Time frame:
Baseline and Week 24
Reported as:
Mean · score on a scale
Change From Baseline in PDAI: Discharge Sub-Score at Week 24
score on a scaleDarvadstrocel 24 mL
Baseline0.9 ± 0.64
Change from Baseline at Week 24-0.4 ± 0.79
SecondaryChange From Baseline in PDAI: Pain Sub-Score at Week 24

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. The pain item is graded on a 5-point scale where 0 indicates no symptoms and 4 indicates severe symptoms and total range of score is from 0 to 4. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

Time frame:
Baseline and Week 24
Reported as:
Mean · score on a scale
Change From Baseline in PDAI: Pain Sub-Score at Week 24
score on a scaleDarvadstrocel 24 mL
Baseline0.9 ± 0.92
Change from Baseline at Week 24-0.6 ± 0.90
SecondaryChange From Baseline in Crohn's Disease Activity Index (CDAI): Total Score at Week 24

CDAI score is calculated from the following 8 items: (a) Number of liquid or very soft stools; (b) Abdominal pain; (c) General wellbeing; (d) Extraintestinal complications; (e) Antidiarrhoeal drugs; (f) Abdominal mass; (g) Hematocrit; and (h) Body weight. Scores of some items in CDAI are calculated based on patient diary. Total score ranges from 0 to 600. Higher score means more severe disease and especially severe disease was defined as a value of greater than 450. Negative change from Baseline indicates improvement.

Time frame:
Baseline and Week 24
Reported as:
Mean · score on a scale
Change From Baseline in Crohn's Disease Activity Index (CDAI): Total Score at Week 24
score on a scaleDarvadstrocel 24 mL
Baseline94.25 ± 60.048
Change from Baseline at Week 24-5.15 ± 47.500
SecondaryChange From Baseline in Van Assche Score at Week 24

The Van Assche score represents the magnetic resonance imaging (MRI)- based severity of perianal lesion associated with Crohn's disease. Based on MRI data, the number, location and extension of fistula tracts, hyperintensity on T2-weighted images, presence or absence of collections (cavities \>3 mm in diameter), and rectal wall involvement will be evaluated. The score range was from 0 to 22. Higher score means more severe disease. Negative change from Baseline indicates improvement.

Time frame:
Baseline and Week 24
Reported as:
Mean · score on a scale
Change From Baseline in Van Assche Score at Week 24
score on a scaleDarvadstrocel 24 mL
Baseline14.5 ± 3.99
Change from Baseline at Week 24-1.7 ± 4.35
SecondaryPercentage of Participants With Combined Remission of Perianal Fistulising CD at Week 52

Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at the screening despite gentle finger compression, and absence of collections \>2 cm in the treated fistulas which is confirmed by the central MRI assessment at Week 52 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point.

Time frame:
Week 52
Reported as:
Number · percentage of participants
Percentage of Participants With Combined Remission of Perianal Fistulising CD at Week 52
percentage of participantsDarvadstrocel 24 mL
Percentage of Participants With Combined Remission of Perianal Fistulising CD at Week 5268.2 (48.7 to 87.6)
SecondaryPercentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 52

Clinical remission is defined as the clinically confirmed closure of all treated external openings that were draining at screening despite gentle finger compression at Week 52 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point.

Time frame:
Week 52
Reported as:
Number · percentage of participants
Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 52
percentage of participantsDarvadstrocel 24 mL
Percentage of Participants With Clinical Remission of Perianal Fistulising CD at Week 5272.7 (54.1 to 91.3)
SecondaryPercentage of Participants With Response of Perianal Fistulising CD at Week 52

Response is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at the screening despite gentle finger compression at Week 52 visit. In case of missing values, LOCF method was applied. Percentages are rounded off to the nearest decimal point.

Time frame:
Week 52
Reported as:
Number · percentage of participants
Percentage of Participants With Response of Perianal Fistulising CD at Week 52
percentage of participantsDarvadstrocel 24 mL
Percentage of Participants With Response of Perianal Fistulising CD at Week 5290.9 (78.9 to 100.0)
SecondaryTime to Combined Remission of Perianal Fistulising CD by Week 52

Time to combined remission is defined as the time from the study product administration to the first visit by which combined remission is observed. Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at the screening despite gentle finger compression, and absence of collections \>2 cm in the treated fistulas which is confirmed by the central MRI assessment.

Time frame:
Up to Week 52
Reported as:
Median · days
Time to Combined Remission of Perianal Fistulising CD by Week 52
daysDarvadstrocel 24 mL
Time to Combined Remission of Perianal Fistulising CD by Week 52175.5 (165.0 to 365.0)
SecondaryTime to Clinical Remission of Perianal Fistulising CD by Week 52

Time to clinical remission is defined as the time from the study product administration to the first visit by which clinical remission is observed. Clinical remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression.

Time frame:
Up to Week 52
Reported as:
Median · days
Time to Clinical Remission of Perianal Fistulising CD by Week 52
daysDarvadstrocel 24 mL
Time to Clinical Remission of Perianal Fistulising CD by Week 5225.5 (14.0 to 109.0)
SecondaryTime to Response of Perianal Fistulising CD by Week 52

Time to response is defined as the time from the study product administration to the first visit by which response is observed. Response is defined as the clinically confirmed closure of at least 50 percent of all treated external openings that were draining at the Screening despite gentle finger compression.

Time frame:
Up to Week 52
Reported as:
Median · days
Time to Response of Perianal Fistulising CD by Week 52
daysDarvadstrocel 24 mL
Time to Response of Perianal Fistulising CD by Week 5218.0 (12.0 to 30.0)
SecondaryPercentage of Participants With Relapse of Perianal Fistulising CD at Week 52 in Participants With Combined Remission at Week 24

Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection \>2 cm in the treated fistulas confirmed by central MRI assessment in participants who achieved combined remission at Week 24. Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression, and absence of collections \>2 cm in the treated fistulas, confirmed by the central MRI assessment. LOCF method was applied. Percentages are rounded off to the nearest decimal point.

Time frame:
Week 52
Reported as:
Number · percentage of participants
Percentage of Participants With Relapse of Perianal Fistulising CD at Week 52 in Participants With Combined Remission at Week 24
percentage of participantsDarvadstrocel 24 mL
Percentage of Participants With Relapse of Perianal Fistulising CD at Week 52 in Participants With Combined Remission at Week 2423.1 (0.2 to 46.0)
SecondaryTime to Relapse of Perianal Fistulising CD by Week 52 in Participants With Combined Remission at Week 24

Time to relapse by Week 52 in participants who achieved combined remission at Week 24 is defined as the time from the combined remission at Week 24 to the first visit by which relapse is observed. Relapse is defined as the clinically confirmed reopening of any of the treated external openings with active drainage, or the development of a collection \>2 cm in the treated fistulas confirmed by central MRI assessment in participants who achieved combined remission at Week 24. Combined remission is defined as the clinically confirmed closure of all treated external openings that were draining at Screening despite gentle finger compression, and absence of collections \>2 cm in the treated fistulas, confirmed by the central MRI assessment.

Time frame:
Up to Week 52
Reported as:
Median · days
Time to Relapse of Perianal Fistulising CD by Week 52 in Participants With Combined Remission at Week 24
daysDarvadstrocel 24 mL
Time to Relapse of Perianal Fistulising CD by Week 52 in Participants With Combined Remission at Week 24NA (NA to NA)
SecondaryChange From Baseline in PDAI: Total Score at Week 52

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) and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

Time frame:
Baseline and Week 52
Reported as:
Mean · score on a scale
Change From Baseline in PDAI: Total Score at Week 52
score on a scaleDarvadstrocel 24 mL
Change From Baseline in PDAI: Total Score at Week 52-2.8 ± 2.59
SecondaryChange From Baseline in PDAI: Discharge Sub-Score at Week 52

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. The discharge item is graded on a 5-point scale ranging from no symptoms (score of 0) to severe symptoms (score of 4) and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

Time frame:
Baseline and Week 52
Reported as:
Mean · score on a scale
Change From Baseline in PDAI: Discharge Sub-Score at Week 52
score on a scaleDarvadstrocel 24 mL
Change From Baseline in PDAI: Discharge Sub-Score at Week 52-0.5 ± 0.95
SecondaryChange From Baseline in PDAI: Pain Sub-Score at Week 52

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. The pain item is graded on a 5-point scale ranging from no symptoms (score of 0) to severe symptoms (score of 4) and total range of score is from 0 to 20. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

Time frame:
Baseline and Week 52
Reported as:
Mean · score on a scale
Change From Baseline in PDAI: Pain Sub-Score at Week 52
score on a scaleDarvadstrocel 24 mL
Change From Baseline in PDAI: Pain Sub-Score at Week 52-0.8 ± 1.06
SecondaryChange From Baseline in CDAI: Total Score at Week 52

CDAI score is calculated from the following 8 items: (a) Number of liquid or very soft stools; (b) Abdominal pain; (c) General wellbeing; (d) Extraintestinal complications; (e) Antidiarrhoeal drugs; (f) Abdominal mass; (g) Hematocrit; and (h) Body weight. Scores of some items in CDAI are calculated based on patient diary. Total score ranges from 0 to 600. Higher score indicates more severe disease and especially severe disease was defined as a value of greater than 450. Negative change from Baseline indicates improvement.

Time frame:
Baseline and Week 52
Reported as:
Mean · score on a scale
Change From Baseline in CDAI: Total Score at Week 52
score on a scaleDarvadstrocel 24 mL
Change From Baseline in CDAI: Total Score at Week 52-20.86 ± 51.331
SecondaryChange From Baseline in Van Assche Total Score at Week 52

The Van Assche score represents the MRI-based severity of perianal lesion associated with Crohn's disease. Based on MRI data, the number, location and extension of fistula tracts, hyperintensity on T2-weighted images, presence or absence of collections (cavities \>3 mm in diameter), and rectal wall involvement will be evaluated. The total score ranges from 0 to 22. Higher score indicates more severe disease. Negative change from Baseline indicates improvement.

Time frame:
Baseline and Week 52
Reported as:
Mean · score on a scale
Change From Baseline in Van Assche Total Score at Week 52
score on a scaleDarvadstrocel 24 mL
Change From Baseline in Van Assche Total Score at Week 52-2.2 ± 4.90

Adverse events

Collected over From first dose of study drug up to Week 156. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Darvadstrocel 24 mL0/22 (0%)11/22 (50%)18/22 (81.8%)
Most frequent serious events
Most frequent serious events
EventDarvadstrocel 24 mL
COVID-19Infections and infestations4/22
Crohn's diseaseGastrointestinal disorders3/22
Anal fistulaGastrointestinal disorders1/22
Calculus urinaryRenal and urinary disorders1/22
Intestinal anastomosis complicationInjury, poisoning and procedural complications1/22
Intestinal obstructionGastrointestinal disorders1/22
Premature labourPregnancy, puerperium and perinatal conditions1/22
Small intestinal obstructionGastrointestinal disorders1/22
Tubulointerstitial nephritisRenal and urinary disorders1/22
Most frequent other events
Showing 10 of 12
Most frequent other events
EventDarvadstrocel 24 mL
ProctalgiaGastrointestinal disorders7/22
Anal fistulaGastrointestinal disorders6/22
NasopharyngitisInfections and infestations6/22
Back painMusculoskeletal and connective tissue disorders3/22
AcrochordonNeoplasms benign, malignant and unspecified (incl cysts and polyps)2/22
CheilitisGastrointestinal disorders2/22
Dental cariesGastrointestinal disorders2/22
FistulaMusculoskeletal and connective tissue disorders2/22
NauseaGastrointestinal disorders2/22
PharyngitisInfections and infestations2/22

Baseline characteristics

Intent to treat (ITT) Population included all participants enrolled in the study.

Age, Continuous
Age, Continuous(years)Darvadstrocel 24 mL
Mean36.4 ± 10.36
Sex: Female, Male
Sex: Female, Male(Participants)Darvadstrocel 24 mL
Female8
Male14
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Darvadstrocel 24 mL
Region of Enrollment
Region of Enrollment(Participants)Darvadstrocel 24 mL
Japan22
Height
Height(centimeters (cm))Darvadstrocel 24 mL
Mean166.0 ± 8.28
Weight
Weight(kilograms (kg))Darvadstrocel 24 mL
Mean68.33 ± 23.102
Body Mass Index (BMI)
Body Mass Index (BMI)(kilogram per square meter (kg/m^2))Darvadstrocel 24 mL
Mean24.59 ± 7.186
Smoking Classification
Smoking Classification(Participants)Darvadstrocel 24 mL
Participants has Never Smoked16
Participants is a Current Smoker2
Participants is an Ex-Smoker4

2 further baseline measures are reported on the registry.

08

Study locations

11 sites
  • Ieda Hospital
    Toyota, Aichi-ken, Japan
  • Fukuoka University Chikushi Hospital
    Chikushino-shi, Fukuoka, Japan
  • Sapporo Higashi Tokushukai Hospital
    Sapporo, Hokkaido, Japan
  • Hyogo College of Medicine
    Nishinomiya, Hyōgo, Japan
  • Yokohama Municipal Citizen's Hospital
    Yokohama, Kanagawa, Japan
  • Mie University Hospital
    Tsu, Mie-ken, Japan
  • Tohoku Rosai Hospital
    Sendai, Miyagi, Japan
  • Tohoku University Hospital
    Sendai, Miyagi, Japan
  • Osaka University Hospital
    Suita, Osaka, Japan
  • JCHO Tokyo Yamate Medical Center
    Shinjuku, Tokyo, Japan
  • Coloproctology Center Takano Hospital
    Kumamoto, Japan
09

References and documents

Publications

  • Mizushima T, Furukawa S, Sahara R, Ohta A, Okita Y, Ito T, Ikeuchi H, Higashi D, Sugita A, Takahashi K, Ogino T, Kiryu S, Nakaya R, Narii N, Yamaguchi T, Watanabe K, Futami K. Long-term safety and efficacy of darvadstrocel for complex perianal fistulas in Japanese adults with Crohn's disease: 3-year follow-up results. Crohns Colitis 360. 2026 Aug 18;8(3):otag090. doi: 10.1093/crocol/otag090. eCollection 2026 Jul. PubMed 42812859 ↗
  • Furukawa S, Mizushima T, Nakaya R, Shibata M, Yamaguchi T, Watanabe K, Futami K. Darvadstrocel for Complex Perianal Fistulas in Japanese Adults with Crohn's Disease: A Phase 3 Study. J Crohns Colitis. 2023 Apr 3;17(3):369-378. doi: 10.1093/ecco-jcc/jjac144. PubMed 36149832 ↗

Study documents

  • Study protocol · Apr 13, 2021
  • Statistical analysis plan · May 9, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: 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.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report

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.

Data sharing details ↗ · vivli.org

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 10, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03706456
Lead sponsor
Takeda
Responsible party
Sponsor
First posted
Oct 16, 2018
Start date
Mar 6, 2019
Primary completion
Jul 20, 2020
Completion
Feb 10, 2023
Results posted
Oct 7, 2021
Last update
Jun 10, 2024

Study contacts

Study Director
study director · Takeda

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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