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NCT Number: NCT07415044

LY4268989 in Adults With Moderately to Severely Active Ulcerative Colitis

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.

Recruiting

Interested in participating?

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Key information

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

GEDYT, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for 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

Treatment and study plan

LY4268989

Drug

Administered orally

Other names: MORF-057, zotemtegrast

Placebo

Drug

Administered orally

Primary outcomes

  1. Percentage of Participants Who Achieve Clinical Remission with Modified Mayo Score (mMS)

    Time frame: Week 10

  2. 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 outcomes

  1. Percentage of Participants Who Achieve Clinical Response with mMS

    Time frame: Week 10

  2. 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

  3. Percentage of Participants Who Achieve Symptomatic Response

    Time frame: Baseline Up to Week 8

  4. 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

  5. Pharmacokinetics (PK): Plasma Concentrations of LY4268989

    Time frame: Baseline Up to Approximately Week 52

  6. Percentage of Participants Who Achieve Clinical Remission Among Participants Who Achieved Clinical Remission with LY4268989 at Week 10

    Time frame: Week 52

Study contacts

Contact information is provided by the study sponsor or research team.

Physicians interested in becoming principal investigators please contact

CONTACT

[email protected]

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

[email protected]

1-317-615-4559

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

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)

Acronym: EMERALD-3

Important dates

Study start
2026
Primary completion
2030
Study completion
2031
First posted
Feb 17, 2026
Registry last updated
Jul 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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