A study of LY4268989 in participants with Moderately to Severely Active Ulcerative Colitis (EMERALD-3)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eli Lilly & Co.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

24 Jun 2026 → ongoing

Decision date (initial)

2026-06-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2025-524404-29-00

WHO UTN

U1111-1333-7508

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Safety, Pharmacokinetic, Pharmacogenetic, Pharmacodynamic

-To evaluate if the 10-week induction efficacy of LY4268989 is superior to placebo as assessed by clinical remission in participants with moderately to severely active UC
-To evaluate if the maintenance efficacy of LY4268989 is superior to placebo at Week 52 (Visit 208) as assessed by clinical remission among participants who achieve clinical response with LY4268989 at Week 10

Conditions and MedDRA coding

Ulcerative Colitis, Active Moderate

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Have had an established diagnosis of ulcerative colitis (UC) for ≥3 months prior to randomization, which includes endoscopic evidence of UC
2. 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
3. Have evidence of UC extending proximal to the rectum
4. 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
5. 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
6. Must meet contraception requirements

Exclusion criteria 6

1. Have a current diagnosis of • Crohn’s disease • Inflammatory Bowel Disease (IBD unclassified) (formerly known as indeterminate colitis), or • primary sclerosing cholangitis
2. Have an inherited immunodeficiency syndrome or known monogenic cause of UC-like colonic inflammation
3. Have had or will need bowel resection or intestinal or intra-abdominal surgery
4. 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 symptomat
5. Have any prior or current evidence of cancer of the the gastrointestinal (GI) tract, or specified lesions with increased risk of GI malignancie
6. Have a diagnosis or history of malignant disease within 5 years prior to randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of Participants Who Achieve Clinical Remission with Modified Mayo Score (mMS) [Time Frame: Week 10] Percentage of Participants Who Achieve Clinical Remission with mMS Among Participants Who Achieved Clinical Response with LY4268989 at Week 10 [Time Frame: Week 52]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eli Lilly & Co.

Sponsor organisation

Eli Lilly & Co.

Address

1 Lilly Corporate Center

City

Indianapolis

Postcode

46285-0001

Country

United States

Scientific contact point

Organisation

Eli Lilly & Co.

Contact name

Lilly Clinical Trials information desk

Public contact point

Organisation

Eli Lilly & Co.

Contact name

Lilly Clinical Trials information desk

Third parties 17

Locations

11 EU/EEA countries · 56 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 349 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications