A clinical study of MK-7240 for the treatment of ulcerative colitis (MK-7240-001)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Decision date (initial)

2024-04-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2025-523766-25-00

WHO UTN

U1111-1296-0203

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants achieving clinical remission per Modified Mayo Score at Week 12

Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants achieving clinical remission per Modified Mayo Score at Week 52

Secondary objectives 28

1. Study 1: To evaluate the safety and tolerability of tulisokibart
2. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants with endoscopic improvement at Week 12
3. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants achieving clinical response per partial modified Mayo score at Week 12
4. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants with histologic-endoscopic mucosal improvement at Week 12
5. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants achieving clinical remission per partial modified Mayo score at Week 12
6. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants achieving clinical response per partial modified Mayo score at Week 2
7. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants achieving endoscopic remission at Week 12
8. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants reporting no bowel urgency at Week 12
9. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants reporting no abdominal pain at Week 12
10. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by proportion of participants achieving Inflammatory Bowel Disease Questionnaire remission at Week 12
11. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the mean change from baseline in Functional Assessment of Chronic Illness Therapy – Fatigue score at Week 12
12. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo in the Diagnostic Assay positive subpopulation as assessed by the proportion of participants achieving clinical remission per modified Mayo score at Week 12 (pooled Study 1+2)
13. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo in the Diagnostic Assay positive subpopulation as assessed by the proportion of participants with endoscopic improvement at Week 12 (pooled Study 1+2)
14. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants achieving histologic-endoscopic remission at Week 12
15. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants with endoscopic improvement at Week 52
16. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants achieving corticosteroid free clinical remission per modified Mayo score at Week 52
17. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants achieving histologic-endoscopic mucosal improvement at Week 52
18. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants achieving clinical remission per partial modified Mayo score at Week 52
19. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants achieving clinical remission per modified Mayo score at both Week 12 and Week 52
20. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants reporting no bowel urgency at Week 52
21. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants reporting no abdominal pain at Week 52
22. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants achieving endoscopic remission at Week 52
23. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants with endoscopic improvement at both Week 12 and Week 52
24. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the proportion of participants achieving histologic-endoscopic remission at Week 52
25. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by proportion of participants achieving Inflammatory Bowel Disease Questionnaire remission at Week 52
26. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo as assessed by the mean change from baseline in Functional Assessment of Chronic Illness Therapy – Fatigue score at Week 52
27. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo in the Diagnostic Assay positive subpopulation as assessed the proportion of participants achieving clinical remission per modified Mayo score at Week 52
28. Study 1: To evaluate the efficacy of tulisokibart compared to Placebo in the Diagnostic Assay positive subpopulation as assessed by the proportion of participants with endoscopic improvement at Week 52

Conditions and MedDRA coding

Ulcerative colitis

Regulatory references

Scientific advice from competent authorities

Swedish Medical Products Agency, European Medicines Agency, Paul-Ehrlich-Institut, MSD Sharp & Dohme GmbH

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Has had ulcerative colitis (UC) (from onset of symptoms) for at least 3 months before randomization
2. Has moderately to severely active UC
3. Has a weight ≥40 kg
4. Satisfies at least 1 of the following criteria: a. Has had an inadequate response or loss of response to 1 or more protocol specified UC treatments; or b. Protocol specified corticosteroid dependence; or c. Has been intolerant to 1 or more protocol specified UC treatment
5. Is on treatment with protocol allowed drugs during the study and meets drug stabilization requirements, as applicable
6. Is of any sex/gender, from 18 to 80 years of age, inclusive
7. A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding and is not a participant of childbearing potential (POCBP); or is a POCBP and uses an acceptable contraceptive method, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) for at least 14 weeks after the last dose of study intervention, has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention, medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy

Exclusion criteria 22

1. Has a diagnosis of Crohn’s Disease (CD) or indeterminate colitis (inflammatory bowel disease (IBD)-undefined) or other types of colitis or enteritis that may confound efficacy assessment
2. Has a current diagnosis of fulminant colitis and/or toxic megacolon
3. Has UC limited to the rectum (i.e, must have evidence of UC extending beyond the rectosigmoid junction, which is ~10 cm from the anal margin)
4. Has a current or impending need for colostomy or ileostomy
5. Has had a total proctocolectomy or partial colectomy
6. Has received fecal microbial transplantation within 4 weeks before randomization
7. Has UC exacerbation requiring hospitalization within 2 weeks before screening
8. Has prior or current evidence of definite colonic dysplasia except for low-grade dysplasia that has been completely removed
9. Has any active or serious infections without resolution after adequate treatment
10. Has had cytomegalovirus infection that resolved less than 4 weeks before screening
11. Has a transplanted organ which requires continued immunosuppression
12. Has a history of cancer (except fully treated non-melanoma skin cell cancers or cervical carcinoma in situ after complete surgical removal) within the last 5 years
13. Is known to be infected with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
14. Has evidence of active tuberculosis (TB), latent TB not successfully treated (per local guidelines), or inadequately treated TB (for participants with history of TB)
15. Has confirmed or suspected COVID-19
16. Has a history of drug or alcohol abuse within 6 months before screening
17. Has had major surgery within 3 months before screening or has a major surgery (i.e, requiring general anesthesia) planned during the study
18. Is currently receiving or is planning to receive total parenteral nutrition at any time during study treatment
19. Has received UC-related antibiotics and has not been on stable doses for at least 14 days before randomization or has discontinued these medications within 14 days of randomization
20. Requires treatment with a therapy that does not adhere to the protocol specified guidance parameters
21. Has received protocol specified prohibited medications
22. Has had prior exposure to tulisokibart or another anti-tumor necrosis factor-like cytokine 1A (TL1A) antibody

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Study 1: Percentage of Participants Achieving Clinical Remission Per Modified Mayo Score (MMS) at Week 12
2. Study 1: Percentage of Participants Achieving Clinical Remission Per MMS at Week 52

Secondary endpoints 29

1. Study 1: Percentage of Participants With One or More Adverse Events (AEs)
2. Study 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE
3. Study 1: Percentage of Participants With Endoscopic Improvement at Week 12
4. Study 1: Percentage of Participants Achieving Clinical Response Per MMS at Week 12
5. Study 1: Percentage of Participants Achieving Histologic-Endoscopic Mucosal Improvement (HEMI) at Week 12
6. Study 1: Percentage of Participants Achieving Clinical Remission Per partial MMS (pMMS) at Week 12
7. Study 1: Percentage of Participants Achieving Clinical Response Per pMMS at Week 2
8. Study 1: Percentage of Participants With Endoscopic Remission at Week 12
9. Study 1: Percentage of Participants Reporting No Bowel Urgency at Week 12
10. Study 1: Percentage of Participants Reporting No Abdominal Pain at Week 12
11. Study 1: Percentage of Participants Achieving Inflammatory Bowel Disease Questionnaire (IBDQ) Remission at Week 12
12. Study 1: Change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score at Week 12
13. Study 1: Percentage of Diagnostic Assay Positive (Dx+) Participants Achieving Clinical Remission Per MMS at Week 12
14. Study 1: Percentage of Dx+ Participants With Endoscopic Improvement at Week 12
15. Study 1: Percentage of Participants Achieving Histologic-Endoscopic Remission (HER) at Week 12
16. Study 1: Percentage of Participants with Endoscopic Improvement at Week 52
17. Study 1: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission Per MMS at Week 52
18. Study 1: Percentage of Participants Achieving HEMI at Week 52
19. Study 1: Percentage of Participants Achieving Clinical Remission Per pMMS at Week 52
20. Study 1: Percentage of Participants Achieving Sustained Clinical Remission Per MMS at Both Week 12 and Week 52
21. Study 1: Percentage of Participants Reporting No Bowel Urgency at Week 52
22. Study 1: Percentage of Participants Reporting No Abdominal Pain at Week 52
23. Study 1: Percentage of Participants With Endoscopic Remission at Week 52
24. Study 1: Percentage of Participants with Sustained Endoscopic Improvement at Both Week 12 and Week 52
25. Study 1: Percentage of Participants Achieving HER at Week 52
26. Study 1: Percentage of Participants Achieving IBDQ Remission at Week 52
27. Study 1: Change from Baseline in FACIT-Fatigue Score at Week 52
28. Study 1: Percentage of Dx+ Participants Achieving Clinical Remission Per MMS at Week 52
29. Study 1: Percentage of Dx+ Participants With Endoscopic Improvement at Week 52

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

​Justin Klaff​

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

​Justin Klaff​

Third parties 5

Locations

19 EU/EEA countries · 137 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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