Efficacy of top-down therapy with mirikizumab versus standard of care with azathioprine in patients with newly diagnosed, moderate-to-severe Crohn’s disease

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]

Decision date (initial)

2026-06-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To test the hypothesis that mirikizumab induction and maintenance therapy is superior to azathioprine/GC in achieving deep remission at Week 52 among patients, moderate-to-severe Crohn’s disease. In this analysis, any step-up from azathioprine to mirikizumab is classified as non-response (step-up rule A).

Conditions and MedDRA coding

Crohn’s disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Given written informed consent prior to any study-specific procedures.
2. Willing and able to complete the scheduled study assessments, including ileocolonoscopy and daily Diary entry.
3. Willing to comply with contraception requirements (as specified in Section 7.7 Contraception requirements).
4. Age 18–75 years.
5. Naïve to thiopurines (azathioprine or 6-mercaptopurine) and methotrexate.
6. Naïve to advanced therapies (targeted biologic or small-molecule therapies) for Crohn’s disease or any other disease.
7. Early disease: Crohn’s disease diagnosed per DGVS/ECCO criteria ≤12 months and ≥4 weeks before Week 0 (randomization).
8. Prior 5-aminosalicylate (5-ASA) and/or oral glucocorticoid therapy with inadequate response, loss of response, or intolerance to the agent(s) received.
9. If receiving systemic GC at screening start: cumulative systemic GC exposure prior to screening start should be ≤8 weeks, and prednisolone ≤20 mg/day (or equivalent) should be stable for ≥2 weeks before screening colonoscopy.
10. Oral budesonide must be discontinued ≥2 weeks before screening colonoscopy. A switch to prednisolone is permitted. Oral mesalamine must be discontinued ≥2 weeks before screening colonoscopy.
11. Evidence of active Crohn’s disease at enrollment, defined as all of the following: a) CDAI 220–500 at screening and Week 0; and b) CRP > ULN and/or fecal calprotectin >250 µg/g measured during screening (Week -8 to Week 0); and c) Endoscopic activity on screening ileocolonoscopy (Week -8 to Week 0): SES-CD ≥4 for ileal-only (L1) disease; or SES-CD ≥6 for ileocolonic/colonic (L2/L3) disease (Eligibility may be based on local read; central read is used for endpoint assessments.).
12. No actively draining fistula at screening and baseline.
13. No prior CD-related surgery.

Exclusion criteria 19

1. Acute severe/fulminant Crohn’s disease requiring immediate inpatient management or urgent surgery at screening (e.g., obstructive complication with imminent surgery, perforation, draining fistula, uncontrolled sepsis/abscess, toxic megacolon).
2. Oral and rectal 5-ASA or rectal steroids treatment within 2 weeks prior to screening colonoscopy.
3. History of malignancy, except for non-melanoma skin cancer that has been successfully treated and considered cured at screening.
4. Planned or foreseeable surgery at or before randomization (Week 0).
5. Known thiopurine methyltransferase deficiency or known inherited mutated nudix hydrolase 15 (NUDT15) gene.
6. Known hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.
7. Diagnosis inconsistent with Crohn’s disease, including ulcerative colitis, indeterminate colitis, microscopic colitis, or other non-CD inflammatory enteropathies.
8. Clinically important active infection, including but not limited to hepatitis B, hepatitis C, HIV/AIDS, or active tuberculosis (TB).
9. Detectable hepatitis B virus (HBV) DNA or hepatitis C virus (HCV) RNA at screening.
10. Latent TB.
11. Planned receipt of live or live-attenuated vaccines (including Bacillus Calmette-Guerin, BCG) during screening or the study.
12. Systemic mycoses or parasitosis.
13. Unstable or uncontrolled illness that could increase risk or confound efficacy assessment, including but not limited to cerebro-cardiovascular, respiratory, gastrointestinal (other than CD), hepatic, renal, endocrine, hematologic, neurological disorders, or active malignancy.
14. Known systemic hypersensitivity to any study drug or any excipient, or prior acute systemic hypersensitivity to monoclonal antibodies that, in the investigator’s judgment, precludes mirikizumab therapy.
15. Women who are pregnant, lactating or planning pregnancy.
16. Employee of Lilly or any of the organizations involved with this study or study site personnel directly affiliated with this study and/or their immediate families.
17. Participation in another interventional clinical trial involving an investigational product or nonapproved use of a drug within the 12 weeks before screening, or concurrent enrollment in any other clinical study or any other type of medical research judged not to be scientifically or medically compatible with this trial.
18. Unwilling or unable to comply with eDiary/data-capture requirements or other study procedures for the duration of the study.
19. Committed to an institution by judicial or administrative order.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients in deep remission at Week 52 (mITT), defined as patient level combination of all of the following: clinical remission: CDAI <150, endoscopic criterion: SES-CD ≤2 with no deep ulcers (central read), steroid-free: no systemic glucocorticoids within 8 weeks prior to Week 52, no IBD-related surgery through Week 52, no actively draining fistula at Week 52 and no new fistula through Week 52, no new clinically relevant stenosis through Week 52.

Investigational products

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

Test 3

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 · 6 investigational sites

By country

Investigational sites

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

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