LY4268989 In Adults With Moderately To Severely Active Ulcerative Colitis

Overview

About this study

The main purpose of this study is to evaluate the safety and effectiveness of LY4268989 when compared to placebo in adult participants with moderately to severely active ulcerative colitis (UC). The study drug will be administered orally.

The study will last up to approximately 108 weeks, excluding screening.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

* Have had an established diagnosis of ulcerative colitis (UC) for ≥3 months prior to randomization, which includes endoscopic evidence of UC
* Have moderately to severely active UC defined by a Modified Mayo Score (mMS) of 5 to 9 with an Endoscopic Score (ES)≥2 confirmed by central reader and rectal bleeding (RB)≥1
* Have evidence of UC extending proximal to the rectum
* Have documented evidence of having had a surveillance colonoscopy within 1 year, or according to local guidelines, to evaluate for polyps, dysplasia, or malignancy, prior to randomization, if the participant has a history of UC symptoms for more than 8 years
* Have an inadequate response to, loss of response to, or intolerance to at least one conventional medication (including corticosteroids) or one advanced therapy (including biologics, Janus Kinase (JAK) inhibitors, or sphingosine-1-phosphate (S1P) immunomodulators). Participants with inadequate response to vedolizumab are excluded
* Must meet contraception requirements

Exclusion Criteria:

* Have a current diagnosis of

* Crohn's disease
* Inflammatory Bowel Disease (IBD unclassified) (formerly known as indeterminate colitis), or
* primary sclerosing cholangitis
* Have an inherited immunodeficiency syndrome or known monogenic cause of UC-like colonic inflammation
* Have had or will need bowel resection or intestinal or intra-abdominal surgery
* Have evidence of toxic megacolon, intra-abdominal abscess, or stricture or stenosis within small bowel or colon that cannot be traversed by a colonoscope or that are symptomatic
* Have any prior or current evidence of cancer gastrointestinal (GI) tract, or specified lesions with increased risk of GI malignancies
* Have a diagnosis or history of malignant disease within 5 years prior to randomization

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 06/10/2026. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Amanda Johnson, M.D.

Contact us for the latest status

Contact information:

Michele Johnson

johnson.michele@mayo.edu

More information

Publications

Publications are currently not available
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CLS-20611876

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