Complex perianal fistulas in adult patients with Crohn's disease
Conditions
Interventions
investigational material(s)
Generic name etc : Darvadstrocel
INN of investigational material : Darvadstrocel
Therapeutic category code : 239 Other agents affecting digestive organs
Dosage and Administ
Sponsors
Takeda Pharmaceutical Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
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) ==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 patient 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 patient 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 naive 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 x upper limit of normal (ULN). 13. The participant who has hepatic impairment defined by both total bilirubin >=1.5 x ULN, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >=2.5 x 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 patient who developed any of the above diseases within 3 months prior to the screening period. 17. The patient who has congenital or acquired immunodeficiency, including patients 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 patients 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Percentage of Participants with Combined Remission of Perianal Fistulising Crohn's disease (CD) at Week 24 Timeframe; Week 24 Combined remission of perianal fistulising CD 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, 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.Efficacy; Percentage of Participants with Clinical Remission of Perianal Fistulising CD at Week 24 Timeframe; Week 24 Clinical remission of perianal fistulising CD is defined as the clinically confirmed closure of all treated external openings that were draining at the screening despite gentle finger compression at Week 24 Visit. In case of missing values, LOCF method was applied. 2.Efficacy; Percentage of Participants with Response of Perianal Fistulising CD at Week 24 Timeframe; 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 the screening despite gentle finger compression at Week 24 Visit. In case of missing values, LOCF method was applied. 3.Efficacy; Time to Clinical Remission of Perianal Fistulising CD by Week 24 Timeframe; Up to 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 the screening despite gentle finger compression. 4.Efficacy; Time to Response of Perianal Fistulising CD by Week 24 Timeframe; Up to Week 24 Time to response is defined as the time from the study product administration to the first visit by which response is observed. 5.Efficacy; Percentage of Participants with Relapse of Perianal Fistulising CD at Week 24 in Participants with Clinical Remission at Previous Visit Timeframe; 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 clinical remission before Week 24. In case of missing values, LOCF method was applied. 6.Efficacy; Time to Relapse of Perianal Fistulising CD by Week 24 in Partici | — |
Countries
Japan
Outcome results
None listed