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Oral LY4268989 for adults with moderate to severe ulcerative colitis.

A Randomized, Multicenter, Double-Blind, Placebo-Controlled Development Program to Evaluate the Efficacy and Safety of LY4268989 (MORF-057) for the Treatment of Adults With Moderately to Severely Active Ulcerative Colitis (EMERALD-3)

Phase 2 Interventional Eli Lilly and Company · NCT07415044

This tests whether an oral medicine called LY4268989 helps adults with moderate to severe ulcerative colitis more than a placebo.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment1431 (estimated)
Ages18 Years to 80 Years
SexAll
SponsorEli Lilly and Company Industry-sponsored
Drugs / interventionsvedolizumab
Locations252 sites (Phoenix, Arizona and 251 other locations)
Trial IDNCT07415044 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional study gives adult participants with centrally confirmed moderate-to-severe ulcerative colitis either LY4268989 or a matching placebo taken by mouth and follows them for up to about 108 weeks (excluding screening). Eligible participants must have had UC for at least 3 months, a Modified Mayo Score of 5–9 with endoscopic score ≥2 and rectal bleeding ≥1, and disease extending beyond the rectum. Participants must also have had an inadequate response, loss of response, or intolerance to at least one conventional or advanced therapy (with inadequate response to vedolizumab excluded). Endoscopic confirmation and routine surveillance colonoscopy history are required where applicable, and study visits occur at participating U.S. sites.

Who should consider this trial

Good fit: Adults with a confirmed diagnosis of moderate-to-severe ulcerative colitis (Modified Mayo Score 5–9, endoscopic score ≥2, rectal bleeding ≥1), disease extending proximal to the rectum, and prior inadequate response or intolerance to at least one conventional or advanced therapy are the intended participants.

Not a fit: People with only mild disease or disease limited to the rectum, and those who are excluded due to prior inadequate response to vedolizumab, are unlikely to benefit from participating in this protocol.

Why it matters

Potential benefit: If successful, LY4268989 could provide a new oral treatment option to reduce inflammation and symptoms in adults with moderate-to-severe ulcerative colitis.

How similar studies have performed: Other oral small-molecule and biologic therapies have shown benefit in ulcerative colitis trials, but LY4268989 is a novel investigational agent and its effectiveness has not yet been proven.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Phoenix, Arizona and 251 other locations

+202 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Ulcerative ColitisUlcerative Colitis, Active ModerateUlcerative Colitis, Active Severe
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.