Open-label Single-arm Study to Assess the Efficacy of Mirikizumab in Patients With Inflammatory Strictures Due to CD

This is an open-label, single-arm, phase 4 study to assess the efficacy of mirikizumab in 18 years of age) with a diagnosis of ileal or ileocolonic CD based upon radiologic, clinical, endoscopic, and histologic evidence with tolerable obstructive symptoms. Participants will be recruited from approximately 25 sites in 3 countries (Canada, the United Kingdom \[UK\] and the United States \[US\]). This study consists of 3 study periods (screening period, open-label treatment period, and safety follow-up). After signing informed consent, potential study participants will be screened over a 5- week screening period, including magnetic resonance enterography (MRE) and ileocolonoscopy to confirm the presence of inflammatory strictures. Eligible participants will receive 900 mg mirikizumab intravenously (IV) on Day 1 every 4 weeks (Q4W) to Week 8, and then 300 mg mirikizumab subcutaneously (SC) Q4W from Week 12 to Week 24. The primary endpoint will be assessed at Week 24. During the screening visit, MRE will be used to confirm the presence of stricture with areas of edema, which represents a specific sign of moderate-to-severe histologic inflammation. Edema appears as areas of high signal intensity on T2 sequences with selective fat suppression. During screening and Week 24 visits, participants will undergo blinded MRE disease activity assessment with the MaRIA and simplified MaRIA (sMaRIA) score and assessment of stricture items. At the same time points, ileocolonoscopy with biopsy collection (2 from the ileum and 2 from each of ascending, transverse, and descending colon and rectum segments, and 2 within \[if feasible\] or as close to the stricture of the terminal ileum as possible; 12 biopsies total) will be performed for blinded endoscopic and histopathologic disease activity assessments with the SES- CD and Robarts Histopathology Index (RHI), respectively. Throughout the study, participants will undergo routine safety assessments at clinic visits, which will include physical examination, clinical laboratory assessment, and recording of serious adverse events (SAEs). At specified time points throughout the study, participants will complete patient-reported items of the CDAI/2-item PRO (PRO2)/ Harvey-Bradshaw Index (HBI), CD Obstructive Score (CDOS), stricture symptom-related questions, fecal Urgency Numerical Rating Scale (UNRS), Patient Global Impressions of Severity (PGI-S), PGI of Change (PGI-C), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and Symptoms and Impacts Questionnaire for CD (SIQ-CD) questionnaires in an electronic study diary for 7 days. Blood samples will be collected during screening and at Weeks 12 and 24 for safety laboratory and C-reactive protein (CRP) assessments. Stool samples will be collected at baseline and Week 24 for assessing fecal calprotectin (FCP) levels. Participants will undergo a safety follow-up visit 4 weeks after the last dose of study treatment for safety assessments and recording of SAEs, severe liver injury (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] 3 × upper limit of normal \[ULN\]), serious infections, and CD- related complications. The safety follow-up visit can be performed by telephone, unless the participant has any ongoing AEs that require follow-up assessment.