Phase 3 Study of Cx601 in Participants With Complex Perianal Fistulising Crohn's Disease
Condition: Complex Perianal Fistulas in Adult Participants With Crohn's Disease
MeSH terms: Crohn Disease; Fistula
Intervention: Darvadstrocel
Intervention description: Darvadstrocel cell suspension for intralesional injection.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility 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) =<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:

          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.