Phase 2 Study of LY4268989 Co-administered with Mirikizumab in Adults with Moderately to Severely Active Ulcerative Colitis

The primary objective is to evaluate the 12-week induction efficacy of LY4268989 co-administered with mirikizumab compared to mirikizumab monotherapy in adults presenting with moderately to severely active ulcerative colitis. This assessment focuses on the therapeutic impact of combination treatment during the initial phase of disease management.

This clinical trial involves 177 participants diagnosed with ulcerative colitis. The study population includes both male and female patients within the specified age ranges defined by codes 3 and 4. Eligible individuals must have an established diagnosis for at least three months and present with moderately-to-severely active disease that extends proximal to the rectum. Participants must have demonstrated an inadequate response, loss of response, or intolerance to conventional therapy, immunomodulators, or advanced therapy. Additionally, those with symptoms exceeding eight years must have completed recent colorectal cancer surveillance in accordance with regional medical guidelines to evaluate for polyps, dysplasia, or malignancy.

This Phase 2, multicenter, randomized, double-blind, active-controlled study is designed to evaluate the 12-week induction efficacy of LY4268989 co-administered with mirikizumab compared to mirikizumab monotherapy in adults with ulcerative colitis. The research methodology involves comparing the co-administration of LY4268989 and mirikizumab against a control group receiving mirikizumab alone. Participants must have a diagnosis of moderately to severely active ulcerative colitis for at least 3 months and demonstrate an inadequate response, loss of response, or intolerance to conventional, immunomodulatory, or advanced therapies. The primary endpoint is the proportion of participants achieving clinical remission at week 12. The study includes a screening period to confirm eligibility based on disease activity and prior colorectal cancer surveillance status. Following randomization, the induction phase lasts for 12 weeks. Specific conditions regarding early termination are not provided in the source data.

Mirikizumab is administered as a solution for injection. The experimental protocol involves two routes of administration: intravenous delivery of 300 mg and subcutaneous administration of 200 mg.

(S)-3-((S)-2-(5-(2-(dimethylamino)ethyl)-2 oxo-4-(trifluoromethyl)pyridin-1(2h)-yl)-4-methylpentanamido)-3-(4-fluoro-2',4',5,6'-tetramethyl-[1,1'-biphenyl]-3-yl)propanoic acid is provided in capsule form for oral administration.

Placebo treatments are utilized to match both the LY4268989 and the mirikizumab components to maintain the double-blind design of the study for ulcerative colitis.

The efficacy of co-administration of LY4268989 and mirikizumab compared to mirikizumab monotherapy is evaluated in adults with moderately to severely active ulcerative colitis. The primary endpoint is the proportion of participants achieving clinical remission as assessed by the modified Mayo Score at week 12.