Ulcerative Colitis
LY4268989 plus mirikizumab for adults with active ulcerative colitis
This Phase 2 study is evaluating the effectiveness and safety of oral LY4268989 given with mirikizumab, compared with mirikizumab alone, in adults with moderately to severely active ulcerative colitis.
Registry title: LY4268989 (MORF-057) Co-Administered With Mirikizumab in Adults With Moderately to Severely Active Ulcerative Colitis:
40 recruiting U.S. sites ↓Study at a glance
- Age
- 18 Years–80 Years
- Treatment
- LY4268989 or Mirikizumab
- Design
- Randomized · Double
- Central study contact
- Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or1-317-615-4559LillyTrials@Lilly.com
- Sponsor
- Eli Lilly and Company
Research question
In adults with moderately to severely active ulcerative colitis, how do the effectiveness and safety of LY4268989 plus mirikizumab compare with mirikizumab alone?
Participant snapshot
Who the study is looking for
- The study is looking for adults ages 18 through 80.
- Participants must have had ulcerative colitis for at least 3 months, supported by endoscopic and histopathology evidence.
- Participants must have moderately to severely active ulcerative colitis confirmed using specified symptom and endoscopy scores.
- Participants must have had an inadequate response, loss of response, or intolerance to at least one specified ulcerative colitis treatment.
Participation overview
What participation may involve
Participation lasts about 118 weeks, including 104 weeks of treatment, and may involve up to 21 visits. Participants receive mirikizumab with either oral LY4268989 or its placebo. What participation may involve: - Take LY4268989 or its placebo by mouth, depending on study assignment. - Receive mirikizumab first through an intravenous infusion and then by injection under the skin. - Complete assessments of stool frequency, rectal bleeding, and endoscopic findings used in the modified Mayo Score. - Participants may be randomized again for Study Period 2 based on response status and initial study group. Participation is expected to last approximately 118 weeks, including 104 weeks of treatment. Participation may include up to 21 visits.
Study interventions
What participants may receive or do
- LY4268989: An investigational drug, also called MORF-057 or zotemtegrast, administered by mouth with mirikizumab.
- Mirikizumab: A drug administered first through an intravenous infusion and then by injection under the skin in both study groups.
- LY4268989 Placebo: An oral placebo used in the group receiving mirikizumab without active LY4268989.
Study design
How the comparison works
This is a Phase 2, parallel-group study comparing LY4268989 plus mirikizumab with mirikizumab plus an LY4268989 placebo. Some participants will be randomized again for Study Period 2. Participants are assigned to study groups at random. The registry also states that responders, and in one group non-responders, will be randomized again for Study Period 2. The study is double-blind: participants and care providers are masked to assigned treatment. The comparison group receives mirikizumab plus an oral LY4268989 placebo, allowing researchers to compare adding active LY4268989 with mirikizumab alone. The placebo applies to LY4268989; participants in that group still receive mirikizumab.
Reported activities
Procedures and tests
- A screening endoscopy is used to confirm the required endoscopic disease-activity score through central review.
- The modified Mayo Score combines participant-reported stool frequency and rectal bleeding with a physician-assessed endoscopic subscore.
- The primary assessment evaluates clinical remission using the modified Mayo Score at Week 12.
- Secondary assessments include clinical response, symptomatic remission, endoscopic improvement, and remission or response at Weeks 12, 24, and 48.
- The study team must confirm documentation of the ulcerative colitis diagnosis, including endoscopic evidence and a supporting histopathology report.
- Participants with more than 8 years of ulcerative colitis symptoms must have the required recent colorectal surveillance documentation.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- Ulcerative colitis must have been diagnosed at least 3 months before baseline, with supporting endoscopic and histopathology evidence.
- Ulcerative colitis must be moderately to severely active, with a modified Mayo Score of 5 to 9, a centrally confirmed endoscopic subscore of at least 2, and rectal bleeding subscore of at least 1.
- Participants with more than 8 years of ulcerative colitis symptoms need documented surveillance colonoscopy within 1 year, or according to applicable local guidelines, before randomization.
- Participants must be up to date on colorectal cancer surveillance under local society guidelines.
- Participants must have had an inadequate response, loss of response, or intolerance to at least one qualifying ulcerative colitis medication.
- Outside the United States, qualifying conventional-treatment history includes corticosteroids or immunomodulators; United States enrollment under this pathway depends on the interim-analysis condition described by the registry.
- Qualifying advanced-treatment history may include failure or intolerance of specified biologic, Janus kinase inhibitor, or sphingosine-1-phosphate receptor inhibitor therapy; prior mirikizumab is excepted from the listed biologic pathway.
Possible reasons someone may not be able to join
- People with a current diagnosis of Crohn's disease, inflammatory bowel disease unclassified, or primary sclerosing cholangitis are excluded.
- People who have had or will need bowel resection or intestinal or intra-abdominal surgery are excluded.
- Toxic megacolon, an intra-abdominal abscess, or a symptomatic or non-traversable intestinal narrowing is exclusionary.
- An adenomatous polyp in a colon area not affected by colitis is exclusionary if it has not been removed; the criterion no longer applies after complete removal if only low-grade dysplasia is found.
- A current or recent acute, active infection is exclusionary.
Important unknowns
What the record does not make clear
- The registry identifies a placebo-containing group but does not report the initial or second-period assignment ratios.
- The registry does not state which current ulcerative colitis medicines may continue during the study.
- Medication washout requirements and their timing are not reported.
- The record does not describe rescue treatment if ulcerative colitis worsens.
- A screening endoscopy and endoscopy-based outcome assessments are described, but the complete number and timing of endoscopies are not reported.
- The registry does not explain which study-related or routine-care costs are covered or billed to insurance.
- Participant compensation is not reported.
- Travel reimbursement or other travel support is not reported.
- The record does not describe access to study treatment after participation ends.
- The overall study is recruiting, but listed sites have different recruitment statuses and local availability may change.
Before contacting the site
Questions for the study team
- What are the assignment chances for active LY4268989 versus placebo in each study period, and how does re-randomization work?
- Which current ulcerative colitis medicines may continue, and are any washout periods required?
- How many endoscopies and other invasive procedures are required, and when are they scheduled?
- What happens if ulcerative colitis worsens or a participant does not respond during either study period?
- Which study-related costs are covered, what might be billed to insurance, and are compensation or travel support available?
- Is the site nearest me actively enrolling the relevant cohort, and which visits must occur in person?
- What treatment access or follow-up is available after the 118-week participation period?
Before changing care
Questions for your gastroenterologist
- How stable is my ulcerative colitis now, and what risks could treatment changes or a washout pose in my case?
- How do the study treatments compare with approved alternatives that remain reasonable for my treatment history?
- Are there infection, surgical, narrowing, polyp, or other clinical concerns in my history that I should discuss with the research team?
- How should my regular gastroenterology care and colorectal cancer surveillance be coordinated with the research team?
- What plan would protect continuity of care if my disease worsens or I stop study treatment?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
The main purpose of the study is to evaluate the effectiveness and safety of LY4268989 when given with mirikizumab compared to mirikizumab alone in adult participants with moderately to severely active ulcerative colitis (UC). Study participation will last approximately 118 weeks, including 104 weeks of treatment and may include up to 21 visits.
Study design and administration
- Organization
- Eli Lilly and Company
- Organization class
- Industry
- Organization study ID
- 27704
- Lead sponsor
- Eli Lilly and Company
- Sponsor class
- Industry
- Enrollment type
- Estimated
- Allocation
- Randomized
- Intervention model
- Parallel
- Primary purpose
- Treatment
- Masking
- Double
- Who is masked
- Participant, Care Provider
- Standard age groups
- Adult, Older Adult
Study arms
Experimental
LY4268989 + Mirikizumab
LY4268989 administered orally (PO) + Mirikizumab administered intravenously (IV), then subcutaneously (SC). Responders will be re-randomized for Study Period 2.
Interventions: Drug: LY4268989, Drug: Mirikizumab
Experimental
Mirikizumab + LY4268989 Placebo
Mirikizumab administered IV, then SC + LY4268989 placebo administered PO. Responders and Non-responders will re-randomized for Study Period 2.
Interventions: Drug: Mirikizumab, Drug: LY4268989 Placebo
Interventions
Drug
LY4268989
Administered PO
Drug
Mirikizumab
Administered IV then SC
Drug
LY4268989 Placebo
Administered PO
Eligibility
18 Years–80 Years
All
Not accepted
Inclusion criteria (12)
- 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 UCRegistry-derived · unreviewed
- Have moderately to severely active UC as defined by a mMS of 5 to 9 with an ES ≥2 confirmed by central reader at screening endoscopy and RB ≥1.Registry-derived · unreviewed
- 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 randomizationRegistry-derived · unreviewed
- Are up-to-date on colorectal cancer surveillance per local society guidelinesRegistry-derived · unreviewed
- Have an inadequate response to, loss of response to, or intolerance to at least 1 of the medications:Registry-derived · unreviewed
- 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)Registry-derived · unreviewed
- 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)Registry-derived · unreviewed
- 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:Registry-derived · unreviewed
- 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 forRegistry-derived · unreviewed
- mirikizumab.Registry-derived · unreviewed
- Janus kinase inhibitors (JAK) such as filgotinib, tofacitinib, or upadacitinibRegistry-derived · unreviewed
- sphingosine 1-phosphate receptor 1 inhibitors (S1PR) such as etrasimod or ozanimodRegistry-derived · unreviewed
Exclusion criteria (9)
- Have a current diagnosis ofRegistry-derived · unreviewed
- Crohn's diseaseRegistry-derived · unreviewed
- Inflammatory Bowel Disease (IBD) unclassified (formerly known as indeterminate colitis), orRegistry-derived · unreviewed
- primary sclerosing cholangitisRegistry-derived · unreviewed
- Have had or will need bowel resection or intestinal or intra-abdominal surgeryRegistry-derived · unreviewed
- 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 symptomaticRegistry-derived · unreviewed
- Have any adenomatous polyp occurring in areas of the colon not involved by colitis, that has not been removedRegistry-derived · unreviewed
- Note: If such an adenomatous polyp has been completely removed and shows only low-grade dysplasia, this criterion would no longer applyRegistry-derived · unreviewed
- Have a current or recent acute, active infectionRegistry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
Percentage of Participants Who Achieve Clinical Remission with Modified Mayo Score (mMS)
Time frame: Week 12
The mMS is a composite score reported by participants and physician and is comprised of the following 3 subscores: Stool Frequency (SF); Rectal Bleeding (RB), and Endoscopic Subscore (ES). Clinical remission (mMS) is defined as: * SF subscore = 0 or 1 and no greater than baseline * RB subscore = 0 * Centrally read ES = 0 or 1; score of 1 modified to exclude friability
Secondary outcome
Percentage of Participants Who Achieve Clinical Response with mMS
Time frame: Week 12
Secondary outcome
Percentage of Participants Who Achieve Endoscopic Improvement
Time frame: Week 12
Secondary outcome
Percentage of Participants Who Achieve Symptomatic Remission
Time frame: Week 12
Secondary outcome
Percentage of Participants Who Achieve Clinical Remission with mMS
Time frame: Week 24
Secondary outcome
Percentage of Participants Who Achieve Clinical Response with mMS
Time frame: Week 24
Secondary outcome
Percentage of Participants Who Achieve Clinical Remission with mMS
Time frame: Week 48
Secondary outcome
Percentage of Participants Who Achieve Clinical Response with mMS
Time frame: Week 48
Secondary outcome
Percentage of Participants Who Achieve Clinical Remission with mMS + Physician's Global Assessment (PGA)
Time frame: Week 48
Secondary outcome
Percentage of Participants Who Achieve Clinical Response with mMS + PGA
Time frame: Week 48
Recruiting locations in the United States
Mayo Clinic in Arizona - Scottsdale
RecruitingScottsdale, Arizona, 85259, United States
Manreet Kaur
Clinnova Research - Anaheim
RecruitingAnaheim, California, 92805, United States
Amit Bhanvadia
Biopharma Informatic, LLC
RecruitingLos Angeles, California, 90035, United States
Morris Silver, MD
Peak Gastroenterology Associates
RecruitingColorado Springs, Colorado, 80907, United States
Bhaktasharan Patel
Encore Borland-Groover Clinical Research
RecruitingJacksonville, Florida, 32256, United States
Kyle Etzkorn
Clinical Research of Osceola
RecruitingKissimmee, Florida, 34741, United States
Basher Atiquzzaman
Florida Research Institute
RecruitingLakewood Rch, Florida, 34211, United States
Manuel Rodriguez
Alliance Medical Research
RecruitingLighthouse PT, Florida, 33064, United States
Vipin Gupta
Digestive and Liver Center of Florida
RecruitingOrlando, Florida, 32825, United States
Harinath Sheela
Center for Gastrointestinal Health - Fairview Heights
Not Yet RecruitingBelleville, Illinois, 62223, United States
SHAKEEL AHMED
Northwestern University
Not Yet RecruitingChicago, Illinois, 60611, United States
Keith Summa
Midtown Gastroenterology and Liver Disease
RecruitingDes Plaines, Illinois, 60016, United States
John Agaiby
GI Alliance - Glenview
RecruitingGlenview, Illinois, 60026, United States
Nina Merel
Gi Alliance - Gurnee
RecruitingGurnee, Illinois, 60031, United States
Jonathan A. Rosenberg
Gastroenterology Health Partners
RecruitingNew Albany, Indiana, 47150, United States
Robert Luckett
Gastroenterology Health Partners
RecruitingLouisville, Kentucky, 40218, United States
Michael Krease
Brigham and Women's Hospital
RecruitingBoston, Massachusetts, 02115, United States
Jessica Allegretti
Clinical Research Institute of Michigan, LLC
RecruitingClinton Township, Michigan, 48038, United States
Mohanad Suede
GI Associates - GIA and Endoscopy Center - Flowood
RecruitingFlowood, Mississippi, 39232, United States
Ralph Vance
Digestive Disease Medicine of Central New York
RecruitingUtica, New York, 13502, United States
Harvey Allen
University Gastroenterology - Providence - West River Street
RecruitingProvidence, Rhode Island, 02904, United States
Jason Ferreira
Gastroenterology Associates, P.A. of Greenville
RecruitingGreenville, South Carolina, 29607, United States
Matthew Barnes
Gastro One - Walnut Run Road
RecruitingCordova, Tennessee, 38018, United States
Ziad Younes
Texas Digestive Disease Consultants - Cedar Park
RecruitingCedar Park, Texas, 78613, United States
Junaid Siddiqui
GI Alliance - Dallas - Gaston Avenue
Not Yet RecruitingDallas, Texas, 75246, United States
Ben Kahn
Southern Star Research Institute
RecruitingSan Antonio, Texas, 78229, United States
Jeff Bullock
Clinical Research Partners, LLC
RecruitingRichmond, Virginia, 23226, United States
Kara Foster-Weiss
Carilion Clinic
RecruitingRoanoke, Virginia, 24014, United States
Lana Wahid
Washington Gastroenterology - Bellevue
RecruitingBellevue, Washington, 98004, United States
Nicholas Procaccini
This study also lists 107 locations outside the United States. They are not shown here.
Central study contacts
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
Contact
Physicians interested in becoming principal investigators please contact
Contact
Registry dates
- First posted
- Sep 22, 2025
- Primary completion
- May 2027
- Overall completion
- Mar 2029
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.