FirST lines of biologics in pAtients with ulceRaTivE colitis: a Randomised controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Hospital Of Clermont-Ferrand

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Decision date (initial)

2026-04-08

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: Diagnosis, Therapy

To compare strategies starting with the use of anti-integrins (vedolizumab), JAK inhibitors (filgotinib), anti-IL12/23 (ustekinumab) or anti-TNF agents (infliximab) as first line of advanced therapy to maintain remission in patients with ulcerative colitis.

Secondary objectives 14

1. To compare the efficacy between the four strategies at 12 months (M12) and M24
2. To compare the safety between the four strategies during the study period
3. To compare the patients' acceptability of the drug regimens between the four strategies
4. To compare the patients' quality of life between the four strategies
5. To compare the patients' disability between the four strategies
6. To compare the efficacy of each drug as first-line therapy
7. To compare the efficacy of each drug as second-line, third-line and fourth-line therapies
8. To compare the efficacy of therapeutic intensification for each drug
9. To compare the safety of each drug
10. To compare the patients' acceptability of each drug
11. To compare the patients' quality of life according to each drug
12. To compare the patients' disability according to each drug
13. To identify predictive factors of efficacy/failure for each medication via a multi-omics approach (proteomics, metagenomics, metabolomics, transcriptomics, genetics, epigenetics, immunophentyping)
14. To identify predictors of venous thromboembolism events

Conditions and MedDRA coding

ulcerative colitis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. - Male or female patients (using effective contraception and a negative pregnancy test for women of childbearing age) diagnosed with UC for at least 3 months
2. - Age ≥ 18 years and ≤ 65 years
3. - Moderate to severe UC according to modified Mayo score (from 5 to 9)
4. - With endoscopic Mayo score ≥ 2
5. - With an inadequate response, failure, loss of response, or intolerance to 5-ASA, steroids, or immunosuppressants.
6. - Patient capable of giving consent
7. - Patient covered by the French healthcare system

Exclusion criteria 18

1. - Usual contra-indication to infliximab, filgotinib, vedolizumab or ustekinumab
2. - Steroids > 20 mg/day within two weeks before inclusion
3. - Low proctitis (disease limited to the rectum with an extent < 5 cm)
4. - Prior history of thromboembolism events
5. - Prior history of major cardiovascular problems (such as heart attack or stroke)
6. - Long-standing smokers (> 40 pack years)
7. - Crohn's disease
8. - Stoma or colectomy
9. - Prior exposure to anti-TNF agents, anti-integrins, anti-interleukines 12 and 23 or JAK inhibitor
10. - Prior exposure to other biologics or experimental drug
11. - No health insurance
12. - Pregnant or lactating women : a pregnancy test will be performed for women of childbearing age
13. - Patients already included in biomedical research other than an observational study (e.g: registry, cohort)
14. - Concomitant Clostridioides difficile infection
15. - HIV infection
16. - Patient who does not master the French language
17. - Patient under guardianship, curatorship or safeguard of justice
18. - Minors

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Remission (composite criteria) = no rectal bleeding, normalization of bowel habits (Mayo sub-score of stool frequency = 0) AND faecal calprotectin < 150 µg/g AND no steroids. Remission will be assessed as a binary criterion (yes/no) each month (i.e. 4 weeks-period) between week 4 and week 52, the month being considered as the statistical unit and not the patient.

Secondary endpoints 22

1. 1) Remission within the first 24 months
2. 2) Absence of symptoms within the first 12 or within the first 24 months (= no rectal bleeding, normalization of bowel habits (Mayo sub-score of stool frequency = 0) and no steroids.
3. 3) Biological remission (defined using levels of faecal calprotectin < 50 μg/g, < 150 μg/g, < 250 μg/g)
4. 4) Endoscopic improvement (mayo endoscopic score (MES) ≤ 1) at W16, W52 and W104
5. 5) Endoscopic remission (MES = 0) at W16, W52 and W104
6. 6) Histological healing (Nancy index ≤ 1) at W16, W52 and W104
7. 7) Clinical remission (total Mayo score ≤ 2 without any subscore >1) at W16, W52 and W104
8. 8) Clinical remission (per Modified Mayo Score) is defined as stool frequency subscore (SFS) ≤1, rectal bleeding subscore (RBS) of 0 and endoscopic subscore ≤1at W16, W52 and W104
9. 9) Histo-endoscopical mucosal improvement (HEMI) (endoscopic improvement and histologic remission) at W16, W52 and W104
10. 10) Histo-endoscopical mucosal healing (HEMH) (endoscopic and histologic remission) at W16, W52 and W104
11. 11) Symptomatic remission (no rectal bleeding and normalization of bowel habits (SF Mayo sub-score ≤ 1) at each visit
12. 12) Level of faecal calprotectin at each visit
13. 13) Rate and number of days spent in clinical remission
14. 14) Acceptability of drug regimen (numerical scale from 0 to 10) at W8, W16, W24, W32, W42, W52, W76 and W104
15. 15) Time to drug failure
16. 16) Time to clinical response including each individual symptoms (rectal bleeding, bowel habits and urgency)
17. 17) Partial Mayo score and simple clinical colitis activity index (SCCAI) at W8, W16, W24, W32, W42, W52, W76 and W104
18. 18) Rate and type of adverse events at W8, W16, W24, W32, W42, W52, W76 and W104
19. 19) Colectomy rate at W8, W16, W24, W32, W42, W52, W76 and W104
20. 20) Quality of life assessed by the IBD questionnaire at W8, W16, W24, W32, W42, W52, W76 and W104
21. 21) Disability assessed by IBD disability index at W8, W16, W24, W32, W42, W52, W76 and W104
22. 22) Disappearance of rectal bleeding, faecal urgency and normalization of bowel habits at W8, W16, W24, W32, W42, W52, W76 and W104.

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Hospital Of Clermont-Ferrand

Sponsor organisation

University Hospital Of Clermont-Ferrand

Address

58 Rue Montalembert

City

Clermont Ferrand Cedex 1

Postcode

63003

Country

France

Scientific contact point

Organisation

University Hospital Of Clermont-Ferrand

Contact name

Lise Laclautre

Public contact point

Organisation

University Hospital Of Clermont-Ferrand

Contact name

Lise Laclautre

Locations

1 EU/EEA country · 29 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 15 files

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

Application history

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