Efficacy of top-down therapy with mirikizumab versus standard of care with azathioprine in patients with newly diagnosed moderate-to-severe ulcerative colitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Schleswig-Holstein AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

5 Dec 2025 → ongoing

Decision date (initial)

2025-09-26

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To test the hypothesis that mirikizumab induction and maintenance therapy (with the possibility of extended induction or re-induction) is superior to azathioprine/glucocorticoids (without step-up treatment) in achieving comprehensive disease control at Week 52 among patients with newly diagnosed moderate-to-severe UC. In this analysis, step-up treatment at any time point in the azathioprine arm is classified as outcome failure due to non-response.

Conditions and MedDRA coding

ulcerative colitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Have given written informed consent prior to any study-specific procedures being completed.
2. Are willing and able to complete the scheduled study assessments, including endoscopy and daily diary entry.
3. Are willing to comply with contraception requirements (as specified in section 7.7)
4. Age between 18 and 75 years.
5. Naïve to azathioprine and its metabolite 6-MP
6. Naïve to advanced therapies.
7. Early disease (duration < 12 months since first diagnosis).
8. Patients with active ulcerative colitis (UC) for whom a previous therapy with 5-aminosalicylic acid (5-ASA) or steroids have not worked well enough, have stopped working, or have caused unacceptable side effects.
9. The steroid oral therapy must have been stable for at least two weeks before baseline and may consist of prednisone ≤20 mg/day (or equivalent) per os.
10. The oral 5-ASA therapy must have been ongoing for at least 8 weeks and dose must be stable for at least 2 weeks before baseline.
11. Modified Mayo score (mMS) 5-9.
12. Endoscopic Mayo (eMayo) score ≥2 (local).
13. Robarts Histopathology Index (RHI) >4 (central).
14. Elevated CRP (above the upper limit of normal) or Fcal (above 250 ug/g stool).
15. Disease localization involving at least the rectum and sigmoid colon (>15 cm).

Exclusion criteria 21

1. Fulminant ulcerative colitis patients who do not respond to steroid treatment or requiring >20 mg of prednisolone (or equivalent) at baseline and/or fulfilling the criteria for severe UC (requirement of hospitalization).
2. Patients with complex UC who have required cyclosporine and tacrolimus for previous treatment.
3. Treatment with MTX within 8 weeks before baseline.
4. Rectal 5-ASA or rectal steroids treatment within 2 weeks prior to baseline.
5. History of malignancy, except for non-melanoma skin cancer.
6. Planned or foreseeable surgery at the time of inclusion.
7. Known thiopurine methyltransferase deficiency.
8. Known hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.
9. Diagnosis of Crohn’s disease.
10. Have been diagnosed with clinically important infection including, but not limited to, hepatitis B, hepatitis C, HIV/AIDS, and active tuberculosis (TB).
11. Have detectable hepatitis B virus (HBV) DNA. or hepatitis C virus (HCV) RNA.
12. Have been diagnosed with latent TB and are not willing to comply with completing TB treatment as appropriate.
13. Intend to receive a Bacillus Calmette-Guerin (BCG) vaccination or live attenuated vaccine(s) during the study.
14. Have been diagnosed with systemic mycoses and parasitosis.
15. Have an unstable or uncontrolled illness, including, but not limited to, cerebro-cardiovascular, respiratory, gastrointestinal (excluding UC), hepatic, renal, endocrine, hematologic or neurological disorders or malignancy that would potentially affect patient safety within the study or confound efficacy assessment.
16. Have a known systemic hypersensitivity to any component of this investigational product or has experienced an acute systemic hypersensitivity event with previous study drug administration, that precludes mirikizumab therapy.
17. Women who are pregnant, lactating or planning pregnancy.
18. Became a Lilly employee or employee of any of the organizations involved with this study or study site personnel directly affiliated with this study and/or their immediate families.
19. Have participated in another clinical trial involving an investigational product or nonapproved use of a drug during the last twelve weeks before screening or are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.
20. Are unwilling or unable to comply with the use of a data collection device to directly record data from the patient daily for the duration of Study MIRACLE or are unable to complete other study procedures.
21. Have been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients achieving comprehensive disease control at Week 52.

Investigational products

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

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Schleswig-Holstein AöR

Sponsor organisation

Universitaetsklinikum Schleswig-Holstein AöR

Address

Arnold-Heller-Strasse 3, Brunswik Brunswik

City

Kiel

Postcode

24105

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Schleswig-Holstein AöR

Contact name

Office Prof. Stefan Schreiber

Public contact point

Organisation

Universitaetsklinikum Schleswig-Holstein AöR

Contact name

Office Prof. Stefan Schreiber

Locations

1 EU/EEA country · 15 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 10 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