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LY4268989 (MORF-057) with mirikizumab for adults with moderate-to-severe ulcerative colitis

A Phase 2, Multicenter, Randomized, Double-Blind, Active-Controlled Study of LY4268989 (MORF-057) Co-Administered With Mirikizumab in Adults With Moderately to Severely Active Ulcerative Colitis

Phase 2 Interventional Eli Lilly and Company · NCT07186101

We will test whether adding LY4268989 to mirikizumab helps adults with moderate-to-severe ulcerative colitis get better control than mirikizumab alone.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment252 (estimated)
Ages18 Years to 80 Years
SexAll
SponsorEli Lilly and Company Industry-sponsored
Drugs / interventionsmirikizumab, filgotinib, tofacitinib, upadacitinib
Locations148 sites (Scottsdale, Arizona and 147 other locations)
Trial IDNCT07186101 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional study compares co-administration of LY4268989 plus mirikizumab against mirikizumab with LY4268989 placebo in adults who have moderately to severely active ulcerative colitis. Eligible participants must have documented endoscopic and histologic evidence of UC and meet specified clinical severity scores confirmed by a central reader. Treatment lasts up to 104 weeks within a total participation time of about 118 weeks and may include around 21 clinic visits. Safety and effectiveness outcomes will be tracked throughout the treatment period.

Who should consider this trial

Good fit: Adults with a confirmed diagnosis of ulcerative colitis for at least 3 months who have moderately to severely active disease (mMS 5–9 with ES ≥2 and RB ≥1) and an inadequate response, loss of response, or intolerance to at least one prior medication are the intended candidates.

Not a fit: Patients with mild ulcerative colitis, those who are well controlled on current therapy, or those who do not meet the study severity or surveillance requirements are unlikely to benefit from this study treatment.

Why it matters

Potential benefit: If successful, the combination could improve symptom control and remission rates beyond mirikizumab alone for adults with moderate-to-severe UC.

How similar studies have performed: Mirikizumab has shown benefit in prior UC studies, but the specific combination of LY4268989 with mirikizumab is investigational and not yet established.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Have had an established diagnosis of UC of ≥3 months in before baseline, which includes endoscopic evidence of UC and a histopathology report that supports a diagnosis of UC
* Have moderately to severely active UC as defined by a mMS of 5 to 9 with an ES ≥2 confirmed by central reader and RB ≥1, with endoscopy performed within 21 days before baseline
* Participants with greater than 8 years of UC symptoms have documented evidence of having had a surveillance colonoscopy within 1 year, or according to local country or regional medical guidelines, to evaluate for polyps, dysplasia, or malignancy, prior to randomization
* Are up-to-date on colorectal cancer surveillance per local society guidelines
* Have an inadequate response to, loss of response to, or intolerance to at least 1 of the medications:
* Conventional-failed participants: Participants who have had an inadequate response to or a loss of response to or are intolerant to at least 1 of the following medications: corticosteroids or immunomodulators (Does not apply to US)

NOTE: After the interim analysis, participants with inadequate response, loss of response, or intolerance to conventional UC therapy without prior exposure to biologics may be enrolled if deemed appropriate (Applies to the US)

* Advanced therapy-failed participants: Participants who have an inadequate response to or a loss of response to, or are intolerant to advanced therapy for UC, defined as:

  * a biologic or biosimilar medication such as anti-tumor necrosis factor (anti-TNF) antibodies or anti-interleukin antibodies (IL-12/23, or IL-23p19), except for

    * mirikizumab.
  * Janus kinase inhibitors (JAK) such as filgotinib, tofacitinib, or upadacitinib
  * sphingosine 1-phosphate receptor 1 inhibitors (S1PR) such as etrasimod or ozanimod

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 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 adenomatous polyp occurring in areas of the colon not involved by colitis, that has not been removed

Note: If such an adenomatous polyp has been completely removed and shows only low-grade dysplasia, this criterion would no longer apply

* Have a current or recent acute, active infection

Where this trial is running

Scottsdale, Arizona and 147 other locations

+98 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 Colitis
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.