Model-informed precision dosing during infliximab rescue therapy for patients with steroid-refractory acute severe ulcerative colitis: an exploratory study (the IGNITE study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Immune System Diseases [C20]

Trial duration

1 Sep 2025 → ongoing

Decision date (initial)

2024-12-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

R-Biopharm

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

• To explore/describe the clinical feasibility of implementing MIPD of infliximab therapy for treating patients with ASUC. [feasibility]
• To explore/describe the accuracy (lack of bias, and precision) of implementing MIPD of infliximab in patients with ASUC. [performance]
• To explore/describe the attainment (including classification accuracy) of (i) the infliximab trough concentration targets and (ii) the model-predicted area under the infliximab concentration-time curve target. [performance]

Secondary objectives 4

1. Effectiveness: to explore/describe the effectiveness of MIPD of infliximab therapy in patients with ASUC.
2. Costs: to explore/describe the costs of MIPD of infliximab therapy in patients with ASUC.
3. [Exploratory]: to explore/describe the user-friendliness of dried bloodspot sampling (DBS).
4. [Exploratory]: to explore/describe the dose-exposure-response relationship of infliximab rescue therapy in patients with ASUC.

Conditions and MedDRA coding

Acute severe ulcerative colitis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. The subject or, when applicable, the subject's legally acceptable representative signs and dates a written informed consent form and any required privacy authorisation prior to or within 48 hours after the initiation of any study procedures.
2. The subject is known with ulcerative colitis and diagnosis confirmed on pathology.
3. The subject is aged 18 years to 75 years (inclusive) at the first infliximab infusion.
4. The subject has a good understanding of the Dutch and/or English language.
5. The subject is admitted with a diagnosis of ASUC defined according to the Truelove and Witts’ criteria.
6. The subject is hospitalised.
7. The subject failed intravenous steroid treatment as defined by the Oxford criteria (more than 8 stools/d or 3-8 stools/d and CRP ≥45) and a Lichtiger score ≥ 10 on day 3 (± 2 days) after starting intravenous steroid treatment.
8. The subject did not receive anti-tumour necrosis factor therapy before.
9. The subject will receive infliximab as rescue therapy for this episode of acute severe ulcerative colitis.
10. The subject will receive a first dose of infliximab, or already received a first dose of 10 mg/kg infliximab within 48 hours before screening and signing the patient consent form (must have blood samples during each day), as rescue therapy for this episode of ASUC.

Exclusion criteria 3

1. The subject has an ostomy or an ileal pouch anal anastomosis.
2. The subject received ciclosporin prior to infliximab as rescue therapy during the same hospitalisation.
3. The subject is participating in another interventional clinical trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. A description of the workload experienced by the healthcare personnel involved in the MIPD process, using the National Aeronautics and Space Association task load index (NASA-TLX, cf. Appendix 1). [feasibility]
2. A relative bias (rBias) within 20% between observation and model prediction, with a 95% confidence interval including zero. [performance]

Secondary endpoints 19

1. colectomy-free survival at 12 weeks (± one week) after start of infliximab therapy (short- term);
2. colectomy-free survival at 24 weeks (± one week) (i.e., the end of the safety follow-up) ;
3. (steroid-free) clinical response at 12 weeks (± one week) after start of infliximab therapy (short-term);
4. (steroid-free) clinical remission at 12 weeks (± one week) after start of infliximab therapy (short-term);
5. biological response at 12 weeks (± one week) after start of infliximab therapy (short-term);
6. biological remission at 12 weeks (± one week) after start of infliximab therapy (short-term);
7. endoscopic response at 12 weeks (± one week) after start of infliximab therapy (short-term);
8. endoscopic remission at 12 weeks (± one week) after start of infliximab therapy (short- term);
9. minimal histological disease activity at 12 weeks (± one week) after start of infliximab therapy (short-term);
10. intestinal ultrasound (IUS) based disease activity during the first 12 weeks after the start of infliximab therapy (short-term)
11. histological remission at 12 weeks (± one week) after start of infliximab therapy (short-term)
12. percentage of target concentration attainment during the first 12 weeks;
13. length of hospital admission after start of infliximab therapy;
14. mortality;
15. relapse-free survival in patients achieving clinical remission;
16. need for rescue therapy other than infliximab;
17. postoperative complications;
18. the total infliximab dose, the number of infliximab infusions, and the direct cost of infliximab therapy during the first 12 weeks (± one week) of the model-guided infliximab rescue therapy.
19. the ratio of the direct cost to the proportion of patients achieving colectomy-free survival at week 12 (± one week) after the start of model-guided infliximab rescue therapy

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Bram Verstockt

Public contact point

Organisation

UZ Leuven

Contact name

Bram Verstockt

Locations

1 EU/EEA country · 1 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 13 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