Phase 2 Randomized Study of LY4395089 Combined with Mirikizumab Versus Mirikizumab Alone in Adults with Moderately to Severely Active Crohn’s Disease

The primary objective is to assess the 12‑week efficacy of the investigational regimen compared with mirikizumab, as determined by endoscopic outcomes in adults with moderately to severely active Crohn’s disease. Demonstrating endoscopic improvement at 12 weeks serves as a surrogate for mucosal healing, which is associated with reduced disease complications and improved long‑term prognosis.

The trial enrolled 33 adult participants of both sexes who met the protocol-defined criteria for moderate to severe inflammatory bowel disease. Eligible individuals required a confirmed diagnosis of Ulcerative Colitis or Crohn’s Disease for at least three months, substantiated by clinical, endoscopic, and histopathological evidence. For Ulcerative Colitis, enrollment required a modified Mayo score of 5–9 with an endoscopic subscore ≥ 2 and rectal bleeding ≥ 1; for Crohn’s Disease, a Crohn’s Disease Activity Index of 220–450 and a centrally read Simple Endoscopic Score for Crohn’s Disease meeting disease‑specific thresholds were required. Participants must have demonstrated an inadequate response, loss of response, or intolerance to at least one corticosteroid, immunomodulator, or advanced therapy. Use of glucagon‑like peptide‑1 receptor agonists or related agents was permitted if the dose remained stable at screening. All screening laboratory values had to fall within protocol‑specified limits. The population comprised patients meeting the master protocol inclusion criteria, with selection based on these clinical and laboratory parameters; lifestyle factors such as diet or physical activity were not specified as enrollment considerations.

The study is a Phase 2, multicenter, randomized, open‑label, active‑controlled trial evaluating the 12‑week efficacy of co‑administration of LY4395089 and mirikizumab versus mirikizumab alone in adults with moderately to severely active Crohn’s disease. After an initial screening visit to confirm diagnosis, disease activity (CDAI ≥ 220 and ≤ 450) and endoscopic severity (centrally read SES‑CD ≥ 6 or ≥ 4), eligible participants are randomized to one of the two treatment arms. Baseline (Visit 2) marks the first dose administration, followed by scheduled follow‑up visits at weeks 4, 8 and 12 for clinical assessment, endoscopic evaluation, laboratory safety monitoring, and drug dispensing. The end‑of‑study visit occurs at week 12, at which the primary endpoint—percentage of participants achieving endoscopic response—is determined. Participant involvement therefore spans approximately 12 weeks from randomization to the final assessment. The trial may be terminated early for participants who discontinue treatment or for whom continuation is deemed medically inappropriate according to protocol‑defined criteria.

The investigational antibody mirikizumab is supplied as a sterile solution for injection intended for intravenous administration. Each dose contains 900 mg of active substance and is delivered by infusion according to the study‑specified schedule.

Mirikizumab is also provided as a sterile solution for injection for subcutaneous use. The subcutaneous formulation is dosed at 300 mg per administration and is given by injection at the intervals defined in the protocol.

LY4395089 is administered orally in tablet form. The tablet contains the active compound ly4395089; the exact dose is defined by the study protocol and is taken by mouth according to the assigned dosing regimen.

The active‑control arm of the study consists of mirikizumab monotherapy administered at the same dosing levels as described for the investigational arms, serving as the comparator for the combination regimen.

All study medications are administered under direct observation by clinical staff to ensure correct dosing and route of delivery. Participants receive written instructions and are required to maintain a dosing diary. Compliance is monitored through scheduled clinic visits, pill counts for the oral tablet, and verification of infusion and injection records.

Efficacy will be evaluated by determining the proportion of participants who achieve predefined endoscopic outcomes at Week 12 of the study. The primary efficacy parameters are endoscopic response for participants with Crohn’s disease and endoscopic improvement for participants with ulcerative colitis.

Endoscopic assessments will be performed at baseline and at the Week 12 time point using colonoscopic examination. The proportion of participants meeting the response or improvement criteria will be calculated and compared between the investigational regimen and the mirikizumab control arm.