Efficacy of Mirikizumab in Achieving Transmural Healing in Patients with Crohn's Disease

The primary objective of this study is to evaluate the efficacy of mirikizumab in achieving transmural response in patients with Crohn's disease. Secondary objectives include:

• Assessment of the efficacy of mirikizumab in achieving transmural healing or a combination of clinical remission and transmural response.
• Evaluation of efficacy regarding bowel urgency, disability, and quality of life.
• Analysis of clinical and biochemical efficacy, including the timing of such responses.
• Investigation of the kinetics of transmural response or healing and the identification of predictors for these outcomes.
• Assessment of drug retention, acceptability, and the impact of therapy on preventing bowel damage progression.
• Evaluation of safety.
• Correlation analysis between faecal calprotectin, CRP, bowel urgency, transmural activity, and PRO-2.

The sponsor did not provide the total number of participants for this study. The investigation involves a population of patients diagnosed with Crohn's disease, including both males and females. The age range for inclusion is between 18 and 75 years. Participants must present with symptomatic disease based on the PRO-2 assessment, defined by a stool frequency greater than 3 or an abdominal pain score greater than 1. Additionally, eligibility requires evidence of transmural inflammation during baseline magnetic resonance imaging, characterized by a C-score exceeding 0.5 in at least one segment.

This phase IV clinical trial is designed to evaluate the efficacy of mirikizumab in achieving transmural response in patients diagnosed with Crohn's disease. The research methodology focuses on assessing the transmural response, defined as a decrease of at least 25% in the C-score across all active segments from baseline to week 24. Study participation involves an initial screening visit to confirm eligibility based on criteria such as age, symptomatic status, and presence of transmural inflammation on MRI. Following screening, subsequent visits are scheduled to monitor clinical and biochemical endpoints, including clinical remission, bowel urgency, and biochemical remission at various intervals such as weeks 4, 8, 12, and 24. Long-term assessments, including bowel damage evaluation via the Lemann Index, are conducted at 6 and 18 months. The total estimated duration of the study period spans from December 2025 to January 2029.

The experimental therapy consists of mirikizumab, which is administered in several pharmaceutical forms. One administration involves a solution for injection provided in a pre-filled pen (100 mg or 100 mg + 200 mg) or a pre-filled syringe (200 mg), delivered via a subcutaneous route at a dose of 300 mg. An alternative administration method uses a solution for infusion, specifically a 300 mg concentrate, delivered via an intravenous route at a dose of 900 mg.

The primary efficacy endpoint is transmural response (TR25), defined as a decrease of at least 25% in the C-score within each and all active segments from baseline to week 24. Secondary endpoints include a composite endpoint combining clinical remission and TR25 at 6 months. Clinical remission is assessed according to PRO-2. Other measures of transmural response include TR50, defined as a minimum 50% decrease in C-score, transmural healing (C-score < 0.5), and complete transmural healing (C-score = 0).

Additional efficacy assessments include:

• Improvement or normalization of bowel urgency using the UNRS and Urgent score, where clinically meaningful improvement is a decrease of 3 points or greater, and BU remission is defined as a UNRS ≤ 2.
• MaRIA assessment at 6 months.
• IUS transmural response or healing at weeks 4, 8, 12, and 24.
• Bowel damage measured by the Lemann Index at 6 and 18 months.
• Clinical response, clinical remission, and biochemical remission at weeks 4, 8, 12, and 24.
• Drug retention, IBD-disability index, and IBDQ.
• Acceptability numerical scale (ANS) using a 10-point scale.