A Study of Darvadstrocel in Adults With Crohn's Disease and Complex Perianal Fistula

Exclusion Criteria

• •1. The participant has lack of clinical response to prior treatment with darvadstrocel, where clinical response is defined as closure of at least 50% of all treated external fistula openings that were draining at baseline despite gentle finger compression or in the case of a unique fistula, a partial closure of the fistula.
• •2. The participant has a history of hypersensitivity or allergies to darvadstrocel or related compounds.
• •3. The participant has a history of hypersensitivity or allergies to penicillin or to aminoglycosides; Dulbecco modified eagle medium; bovine serum; local anesthetics or gadolinium.
• •4. The participant is currently participating in a double-blind clinical study with darvadstrocel. Participants participating in the ongoing INSPIRE registry (Alofisel-5003) study would need to withdraw from that study in order to enroll in this study.
• •5. The participant is currently receiving or has received any other investigational medicinal product (IMP) within the last 3 months or at least 5 times the respective elimination half-life time, whichever is longer, before signing the ICF.
• •6. 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.
• •a) 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.
• •7. The participant has major alterations in any of the following laboratory tests:
• •1. Serum creatinine levels \>1.5 times the upper limit of normal (ULN).
• •2. Total bilirubin \>1.5 × ULN.
• •3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3.0 × ULN.
• •4. Hemoglobin \<10.0 grams per deciliter (g/dL).
• •5. Platelets \<75.0 × 10\^9 per liter (/L).
• •6. Albumin \<3.0 g/dL.
• •8. The participant has an increased risk for a surgical procedure.
• •9. The participant has a known chronically active hepatopathy of any origin, including cirrhosis and participants with persistent positive hepatitis B surface antigen and quantitative hepatitis B virus polymerase chain reaction (PCR) or positive serology for hepatitis C virus (HCV) and quantitative HCV PCR within 6 months before the baseline visit.
• •10. If female, the participant is pregnant or breastfeeding, or intending to become pregnant before participating in this study, during the study, or intending to donate ova during such time period.
• •11. If male, the participant intends to donate sperm during this study.
• •12. The participant has a contraindication to MRI scan (e.g., due to the presence of pacemaker, hip replacement, severe claustrophobia, or renal insufficiency as defined by local clinical guidelines).
• •13. The participant has a contraindication to the anesthetic procedure.
• •14. The participant has severe rectal and/or anal stenosis that would make it impossible to follow the surgery procedure.
• •15. The participant has severe proctitis (rectal ulcers \>0.5 cm) that would make it impossible to follow the surgery procedure.
• •16. The participant has any prior invasive malignancy diagnosed within the last 3 years before baseline visit. Participants with basal cell carcinoma of the skin completely resected outside the perineal region can be included.
• •17. The participant has a current or recent (within 6 months before the baseline visit) history of severe, progressive, and/or uncontrolled hepatic, hematologic, gastrointestinal (other than CD), renal, endocrine, pulmonary, cardiac, neurologic, or psychiatric disease that may result in participant's increased risk from study participation and/or lack of compliance with study procedures.
• •18. The participant has had major surgery of the gastrointestinal tract within 6 months before baseline or any minor surgery of the gastrointestinal tract 3 months before baseline.
• •19. The participant had local major perianal surgery, and/or treatment with darvadstrocel within 6 months before baseline. The abscess drainage, cleaning surgery, or seton placement are not considered as "local major surgery" in this protocol.
• •20. The participant does not wish to or cannot comply with study procedures.