Ulcerative Colitis, Active Moderate · Ulcerative Colitis, Active Severe · Ulcerative Colitis (UC)
Oral LY4268989 for Adults With Moderately to Severely Active Ulcerative Colitis
This study is comparing the safety and effectiveness of oral LY4268989 with placebo in adults with moderately to severely active ulcerative colitis.
Registry title: LY4268989 in Adults With Moderately to Severely Active Ulcerative Colitis
50 recruiting U.S. sites ↓Study at a glance
- Age
- 18 Years–80 Years
- Treatment
- LY4268989 or Placebo
- 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
How do the safety and effectiveness of oral LY4268989 compare with placebo in adults with moderately to severely active ulcerative colitis?
Participant snapshot
Who the study is looking for
- The study is looking for adults ages 18 through 80.
- The study is looking for people with ulcerative colitis diagnosed at least 3 months before randomization and supported by endoscopic evidence.
- The study is looking for moderately to severely active disease that extends beyond the rectum and meets specified Modified Mayo, endoscopy, and rectal-bleeding thresholds.
- The study is looking for people whose disease did not respond adequately, stopped responding, or was not tolerated with at least one specified conventional or advanced therapy; inadequate response to vedolizumab is an exclusion.
Participation overview
What participation may involve
Participants are randomly assigned to oral LY4268989 at one of two study doses or to oral placebo, with ulcerative-colitis outcomes assessed during the study. What participation may involve: - Take LY4268989 or placebo orally according to the assigned study group. - Undergo assessments of clinical remission, clinical response, symptoms, and the Modified Mayo Score at specified study time points. - Provide plasma samples for measurement of LY4268989 concentrations through approximately week 52. - Participants who do not respond at week 10 will receive open-label LY4268989 in the maintenance study. The registry states that the study may last up to approximately 108 weeks, not including screening.
Study interventions
What participants may receive or do
- LY4268989: An oral study drug, also called MORF-057 or zotemtegrast, given at one of two study doses.
- Placebo: An oral placebo used as the comparison intervention.
Study design
How the comparison works
This Phase 2 treatment study randomly assigns participants to parallel groups receiving one of two oral LY4268989 doses or oral placebo. Assignment is randomized, but the registry does not report the assignment ratios. The study is double-blind: participants and care providers are masked to assigned treatment. The registry states that week-10 nonresponders will receive open-label LY4268989 in the maintenance study. Oral placebo is the control used to compare outcomes with LY4268989. One study group receives oral placebo, but the chance of assignment to that group is not reported.
Reported activities
Procedures and tests
- Modified Mayo Score assessments are used to evaluate clinical remission and response.
- Disease activity must include an endoscopic score of at least 2 confirmed by a central reader and a rectal-bleeding score of at least 1.
- Screening may involve confirming an established ulcerative-colitis diagnosis with endoscopic evidence.
- For people with more than 8 years of ulcerative-colitis symptoms, screening may confirm documentation of a surveillance colonoscopy performed within 1 year or according to local guidelines.
- Plasma concentrations of LY4268989 are measured from baseline through approximately week 52.
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 randomization and include endoscopic evidence.
- Disease must be moderately to severely active, with a Modified Mayo Score of 5 to 9, an endoscopic score of at least 2 confirmed centrally, and a rectal-bleeding score of at least 1.
- Ulcerative colitis must extend beyond the rectum.
- If ulcerative-colitis symptoms have been present for more than 8 years, documentation of a surveillance colonoscopy within 1 year or according to local guidelines is required before randomization.
- There must be an inadequate response, loss of response, or intolerance to at least one specified conventional medication or advanced therapy; people whose inadequate response was to vedolizumab are excluded.
- Participants must meet the study's contraception requirements.
- Participants must be 18 through 80 years old.
Possible reasons someone may not be able to join
- A current diagnosis of Crohn's disease, inflammatory bowel disease unclassified, or primary sclerosing cholangitis excludes participation.
- An inherited immunodeficiency syndrome or known single-gene cause of ulcerative-colitis-like inflammation excludes participation.
- Having had, or being expected to need, bowel resection or intestinal or intra-abdominal surgery excludes participation.
- Toxic megacolon, an intra-abdominal abscess, or a symptomatic or non-traversable bowel stricture or stenosis excludes participation.
- Any previous or current gastrointestinal cancer, or specified lesions associated with increased gastrointestinal cancer risk, excludes participation.
- A diagnosis or history of malignant disease within 5 years before randomization excludes participation.
Important unknowns
What the record does not make clear
- The registry does not state how many visits are required, how often they occur, or which are in person.
- The registry lists two LY4268989 groups and one placebo group but does not report assignment ratios.
- The registry does not explain which current ulcerative-colitis treatments may continue during the study.
- No medication washout periods are reported.
- The registry does not describe permitted rescue treatment if symptoms worsen.
- Eligibility requires endoscopic evidence and a centrally confirmed endoscopic score, but the registry does not state the number or timing of study-required endoscopies.
- The registry does not identify which study-related or routine-care costs are covered.
- The registry does not report whether participants receive compensation.
- The registry does not report reimbursement or support for travel, lodging, or parking.
- The registry does not state whether any visits or assessments may be completed remotely.
- The registry does not describe access to LY4268989 after study participation ends.
- The study is recruiting overall, but individual locations have recruiting, not-yet-recruiting, or suspended statuses.
Before contacting the site
Questions for the study team
- How many visits are required, how often do they occur, and which must be in person?
- What is the chance of assignment to placebo, and how long could placebo treatment continue?
- Which current ulcerative-colitis medicines can continue, and are any washout periods required?
- Which endoscopies or colonoscopies are required by the study, and when will they occur?
- What happens if symptoms worsen, and which rescue treatments are permitted?
- What happens after week 10 for responders and nonresponders, including treatment assignment and masking?
- Which costs are covered, and is compensation or travel support available?
- Is the location and study group relevant to me currently recruiting?
Before changing care
Questions for your gastroenterologist
- How stable is my ulcerative colitis now, and what clinical concerns would you have about possible study participation?
- How could changing or pausing my current treatment affect disease control, and how should any transition be managed?
- What approved treatment alternatives should I consider alongside learning about this study?
- How should you and the research team coordinate endoscopy results, surveillance needs, medicines, and care if my symptoms worsen?
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 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.
Study design and administration
- Organization
- Eli Lilly and Company
- Organization class
- Industry
- Organization study ID
- 27589
- 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 Study Dose 1
LY4268989 administered orally
Interventions: Drug: LY4268989
Experimental
LY4268989 Study Dose 2
LY4268989 administered orally
Interventions: Drug: LY4268989
Placebo Comparator
Placebo Study Dose
Placebo administered orally
Interventions: Drug: Placebo
Interventions
Drug
LY4268989
Administered orally
Drug
Placebo
Administered orally
Eligibility
18 Years–80 Years
All
Not accepted
Inclusion criteria (6)
- Have had an established diagnosis of ulcerative colitis (UC) for ≥3 months prior to randomization, which includes endoscopic evidence of UCRegistry-derived · unreviewed
- 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)≥1Registry-derived · unreviewed
- Have evidence of UC extending proximal to the rectumRegistry-derived · unreviewed
- 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 yearsRegistry-derived · unreviewed
- 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 excludedRegistry-derived · unreviewed
- Must meet contraception requirementsRegistry-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 an inherited immunodeficiency syndrome or known monogenic cause of UC-like colonic inflammationRegistry-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 prior or current evidence of cancer gastrointestinal (GI) tract, or specified lesions with increased risk of GI malignanciesRegistry-derived · unreviewed
- Have a diagnosis or history of malignant disease within 5 years prior to randomizationRegistry-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 10
Primary outcome
Percentage of Participants Who Achieve Clinical Remission with mMS Among Participants Who Achieved Clinical Response with LY4268989 at Week 10
Time frame: Week 52
Secondary outcome
Percentage of Participants Who Achieve Clinical Response with mMS
Time frame: Week 10
Secondary outcome
Percentage of Participants Who Achieve Clinical Response with mMS Among Participants Who Achieved Clinical Response with LY4268989 at Week 10
Time frame: Week 10 Up to Week 52
Secondary outcome
Percentage of Participants Who Achieve Symptomatic Response
Time frame: Baseline Up to Week 8
Secondary outcome
Percentage of Participants Who Achieve Symptomatic Response Among Participants Who Achieved Clinical Response with LY4268989 at Week 10
Time frame: Week 10 Up to Week 52
Secondary outcome
Pharmacokinetics (PK): Plasma Concentrations of LY4268989
Time frame: Baseline Up to Approximately Week 52
Secondary outcome
Percentage of Participants Who Achieve Clinical Remission Among Participants Who Achieved Clinical Remission with LY4268989 at Week 10
Time frame: Week 52
Recruiting locations in the United States
Valleywise Health Medical Center
RecruitingPhoenix, Arizona, 85008, United States
Indu Srinivasan
Clinnova Research
RecruitingAnaheim, California, 92805, United States
Amit Bhanvadia
GMC Clinical Research
RecruitingFolsom, California, 95630, United States
Nazir Rahim
Peak Gastroenterology Associates
RecruitingColorado Springs, Colorado, 80907, United States
Bhaktasharan Patel
Rocky Mountain Gastroenterology Associates - Lakewood
RecruitingLakewood, Colorado, 80228, United States
Rajesh Jain
Medical Research Center of Connecticut
Not Yet RecruitingHamden, Connecticut, 06518, United States
Paul Feuerstadt
K2 Medical Research - Daytona Beach
RecruitingDaytona Beach, Florida, 32114, United States
Esteban Olivera
Clinical Research of Osceola
RecruitingKissimmee, Florida, 34741, United States
Basher Atiquzzaman
Florida Research Institute
RecruitingLakewood Rch, Florida, 34211, United States
Manuel Rodriguez
AdventHealth Orlando
Not Yet RecruitingOrlando, Florida, 32803, United States
Jennifer Seminerio Diehl
Treasure Valley Medical Research
RecruitingBoise, Idaho, 83706, United States
Neetu Talreja
Grand Teton Research Group
RecruitingIdaho Falls, Idaho, 83404, United States
Todd Williams
Northwestern University
Not Yet RecruitingChicago, Illinois, 60611, United States
Keith Summa
Rush University Medical Center
Not Yet RecruitingChicago, Illinois, 60612, United States
Atsushi Sakuraba
Midwest Digestive Health & Nutrition
RecruitingDes Plaines, Illinois, 60016, United States
Amar Naik
Springfield Clinic - First
RecruitingSpringfield, Illinois, 62702, United States
Rajan Kochar
Gastroenterology Health Partners
RecruitingNew Albany, Indiana, 47150, United States
Jonathan Obert
Gastroenterology Health Partners
RecruitingLouisville, Kentucky, 40218, United States
Michael Krease
GI Alliance - Gastro Group and Endocenter - Mandeville
RecruitingMandeville, Louisiana, 70471, United States
Brandon Brousse
Gastroenterology Associates of Western Michigan, PLC d.b.a. West Michigan Clinical Research Center
RecruitingWyoming, Michigan, 49519, United States
Allan Coates
Mayo Clinic in Rochester, Minnesota
Not Yet RecruitingRochester, Minnesota, 55905, United States
Amanda Johnson
KAD Clinical Research
RecruitingSt Louis, Missouri, 63123, United States
Adrian Di Bisceglie
Specialists in Gastroenterology
Not Yet RecruitingSt Louis, Missouri, 63141, United States
Benjamin Root
Digestive Disease Specialists - Las Vegas - Crimson Canyon Drive
RecruitingLas Vegas, Nevada, 89128, United States
Michael Zimmerman
Virtua Health & Wellness Center - Moorestown
Not Yet RecruitingMoorestown, New Jersey, 08057, United States
Sanket Patel
Saint Peter's University Hospital
RecruitingNew Brunswick, New Jersey, 08901, United States
Arkady Broder
Stony Brook University
Not Yet RecruitingStony Brook, New York, 11794, United States
Lasha Gogokhia
Carolina Digestive Diseases and Endoscopy Center
RecruitingGreenville, North Carolina, 27834, United States
Phillip Goldstein
Wilmington Health, PLLC
RecruitingWilmington, North Carolina, 28401, United States
Ashok Shiani
Ohio State University
Not Yet RecruitingHilliard, Ohio, 43026, United States
Jacob Skeans
DSI Research, LLC d/b/a ObjectiveHealth Clinical Research - Springboro
Not Yet RecruitingSpringboro, Ohio, 45066, United States
Anjali Morey
Gastro Intestinal Research Institute of Northern Ohio, LLC
RecruitingWestlake, Ohio, 44145, United States
Mohamed Naem
The Oregon Clinic
Not Yet RecruitingPortland, Oregon, 97220, United States
Phillip Kiyasu
Medical University of South Carolina
Not Yet RecruitingCharleston, South Carolina, 29425, United States
Erin Forster
Sanford USD Medical Center
Not Yet RecruitingSioux Falls, South Dakota, 57105, United States
Ahmed Kurdi
Skyline Gastroenterology of West Tennessee
Not Yet RecruitingJackson, Tennessee, 38301, United States
Brittain Little
Integrity Advanced Therapeutics
RecruitingHouston, Texas, 77090, United States
Howard Hamat
Southern Star Research Institute
RecruitingSan Antonio, Texas, 78229, United States
Jeff Bullock
Eximia Research-VA, LLC
RecruitingNorfolk, Virginia, 23502, United States
John Smith
Swedish Medical Center
Not Yet RecruitingSeattle, Washington, 98104, United States
Jason Harper
Principle Research Solutions
RecruitingSpokane, Washington, 99202, United States
Harold Preiksaitis
Providence Sacred Heart Medical Center & Children's Hospital
Not Yet RecruitingSpokane, Washington, 99208, United States
Eashen Liu
Washington Gastroenterology - Tacoma
RecruitingTacoma, Washington, 98405, United States
William Holderman
This study also lists 207 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
- Feb 17, 2026
- Primary completion
- Jun 2030
- Overall completion
- Jul 2031
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.