Efficacy of Top-down Therapy With Mirikizumab Versus Standard of Care With Azathioprine in Patients With Newly Diagnosed, Moderate-to-severe Crohn's Disease

Prior treatment

• Oral and rectal 5-ASA or rectal steroids treatment within 2 weeks prior to screening colonoscopy.
• Planned or foreseeable surgery at or before randomization (Week 0).
• Planned receipt of live or live-attenuated vaccines (including Bacillus Calmette-Guerin, BCG) during screening or the study.
• Known systemic hypersensitivity to any study drug or any excipient, or prior acute systemic hypersensitivity to monoclonal antibodies that, in the investigator's judgment, precludes mirikizumab therapy.
• Participation in another interventional clinical trial involving an investigational product or nonapproved use of a drug within the 12 weeks before screening, or concurrent enrollment in any other clinical study or any other type of medical research judged not to be scientifically or medically compatible with this trial.

Other illness

• Acute severe/fulminant Crohn's disease requiring immediate inpatient management or urgent surgery at screening (e.g., obstructive complication with imminent surgery, perforation, draining fistula, uncontrolled sepsis/abscess, toxic megacolon).
• History of malignancy, except for non-melanoma skin cancer that has been successfully treated and considered cured at screening.
• Diagnosis inconsistent with Crohn's disease, including ulcerative colitis, indeterminate colitis, microscopic colitis, or other non-CD inflammatory enteropathies.
• Clinically important active infection, including but not limited to hepatitis B, hepatitis C, HIV/AIDS, or active tuberculosis (TB).
• Detectable hepatitis B virus (HBV) DNA or hepatitis C virus (HCV) RNA at screening.
• Unstable or uncontrolled illness that could increase risk or confound efficacy assessment, including but not limited to cerebro-cardiovascular, respiratory, gastrointestinal (other than CD), hepatic, renal, endocrine, hematologic, neurological disorders, or active malignancy.

Lab values

• Known hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.

Other

• Known thiopurine methyltransferase deficiency or known inherited mutated nudix hydrolase 15 (NUDT15) gene.
• Latent TB.
• Systemic mycoses or parasitosis.
• Women who are pregnant, lactating or planning pregnancy
• Employee of Lilly or any of the organizations involved with this study or study site personnel directly affiliated with this study and/or their immediate families.
• Unwilling or unable to comply with eDiary/data-capture requirements or other study procedures for the duration of the study.
• Committed to an institution by judicial or administrative order.

• Given written informed consent prior to any study-specific procedures.
• Willing and able to complete the scheduled study assessments, including ileocolonoscopy and daily Diary entry.
• Willing to comply with contraception requirements (as specified in Section 7.7 Contraception requirements).
• Age 18-75 years.
• Naïve to thiopurines (azathioprine or 6-mercaptopurine) and methotrexate.
• Naïve to advanced therapies (targeted biologic or small-molecule therapies) for Crohn's disease or any other disease.
• Early disease: Crohn's disease diagnosed per DGVS/ECCO criteria ≤12 months and ≥4 weeks before Week 0 (randomization).
• Prior 5-aminosalicylate (5-ASA) and/or oral glucocorticoid therapy with inadequate response, loss of response, or intolerance to the agent(s) received.
• If receiving systemic GC at screening start: cumulative systemic GC exposure prior to screening start should be ≤8 weeks, and prednisolone ≤20 mg/day (or equivalent) should be stable for ≥2 weeks before screening colonoscopy.
• Oral budesonide must be discontinued ≥2 weeks before screening colonoscopy. A switch to prednisolone is permitted. Oral mesalamine must be discontinued ≥2 weeks before screening colonoscopy.
• Evidence of active Crohn's disease at enrollment, defined as all of the following:
  • CDAI 220-500 at screening and Week 0; and
  • CRP \> ULN and/or fecal calprotectin \>250 μg/g measured during screening (Week -8 to Week 0); and
  • Endoscopic activity on screening ileocolonoscopy (Week -8 to Week 0)
• No actively draining fistula at screening and baseline.
• No prior CD-related surgery