Early mirikizumab versus azathioprine for newly diagnosed moderate-to-severe ulcerative colitis

Efficacy of Top-down Therapy With Mirikizumab Versus Standard of Care With Azathioprine in Patients With Newly Diagnosed Moderate-to-severe Ulcerative Colitis: A 52-week, Multicenter, Open-label, Randomized Controlled Trial

This trial will test whether starting mirikizumab right away instead of beginning with azathioprine helps people newly diagnosed with moderate-to-severe ulcerative colitis who did not respond well to mesalazine and steroids.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: University Hospital Schleswig-Holstein (Academic / other)
• Drugs / interventions: mirikizumab, prednisone
• Locations: 1 site (Kiel)
• Trial ID: NCT07235904 on ClinicalTrials.gov

What this trial studies

This interventional Phase 4 trial compares an early “top-down” approach using mirikizumab with the usual azathioprine-based standard of care in patients diagnosed with moderate-to-severe ulcerative colitis within the past 12 months. Participants must be 18–75, naive to azathioprine and advanced therapies, and have had inadequate response to 5-ASA and/or steroids; they will undergo scheduled assessments including endoscopy and daily symptom diaries. Patients assigned to standard therapy may switch to mirikizumab at predefined times during the course of the study. The aim is to determine if earlier use of mirikizumab leads to better disease control and potentially fewer side effects than the traditional step-up approach.

Who should consider this trial

Good fit: Adults aged 18–75 with a UC diagnosis within the last 12 months who have not had adequate response to 5-ASA and steroids and who are naive to azathioprine and other advanced therapies are ideal candidates.

Not a fit: People with long-standing disease (>12 months), prior exposure to azathioprine or biologics, or those with only mild UC are unlikely to be helped by this specific study approach.

Why it matters

Potential benefit: If successful, early mirikizumab could lead to better long-term disease control and fewer side effects compared with starting treatment with azathioprine first.

How similar studies have performed: Recent studies suggest earlier biologic therapy, including mirikizumab, may improve outcomes and reduce side effects compared with delayed use, but direct comparisons of mirikizumab as first-line top-down therapy remain limited.

Eligibility criteria

Inclusion Criteria:

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:

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, cerebrocardiovascular, 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

Where this trial is running

Kiel

• University Hospital Schleswig-Holstein — Kiel, Germany (Recruiting)

Conditions Ulcerative Colitis