Methotrexate in paediatric and adolescent Crohn’s disease: an observational study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Decision date (initial)

2026-04-11

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

MDL Fonds

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic

[PK] Determination of MTX-PG concentrations and identification of accumulation patterns over time in RBCs.
[PD] Association of MTX-PG concentration with MTX discontinuation due to a lack of efficacy or toxicity.

Secondary objectives 11

1. [PK] Identification of clinical determinants influencing MTX-PG accumulation patterns over time in RBCs.
2. [PK] Determination of MTX-PG concentrations in different cells: RBCs versus PBMCs.
3. [PK] Identification of genetic and metabolic determinants related to MTX-PG accumulation patterns over time in RBCs.
4. [PK] Identification of faecal microbiome and metabolome and the association with MTX-PG accumulation patterns
5. [PD] Association of MTX MTX-PG concentration with MTX discontinuation due to a lack of efficacy and determination of a cut-off for responders.
6. [PD] Association of MTX MTX-PG concentration with MTX discontinuation due to toxicity (hematological and hepatic as well as gastrointestinal using the MISS-questionnaire).
7. Constructing a model to predict MTX efficacy during the first year of treatment.
8. Prediction of MTX toxicity before the start of MTX treatment.
9. [PK combination therapy] Association of infliximab dosage and time on MTX-PG accumulation patterns over time in RBCs.
10. [PK combination therapy] Determine the association between MTX-PG concentration and infliximab levels.
11. [PK combination therapy] Determine the association between MTX-PG concentration and anti-drug-antibodies.

Conditions and MedDRA coding

Crohn’s disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age of 4-28 years
2. Written informed consent of patient (if indicated) and parents (if indicated) has been obtained
3. Proven diagnosis of Crohn’s disease based on endoscopic, radiological and histologic findings
4. Will start MTX treatment monotherapy or combination therapy with infliximab

Exclusion criteria 4

1. Not eligible to receive MTX, as in usual care
2. Co-treatment with a biologic agent other than infliximab
3. Inability to read and understand the patient and family information sheets
4. Informed consent of patient has not been obtained when required

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. [PK] RBC MTX-PG levels at 1,3 and 6 months [PD] Drug survival; defined as the cumulative incidence of MTX monotherapy discontinuation during the first year due to treatment failure and/or toxicity. Treatment failure includes need for systemic corticosteroids, biologicals, JAK inhibitors, thiopurine therapy and/or surgery due to CD inflammation because of a flare of CD. Locally applied corticosteroids or dose escalation of MTX will not be considered as treatment failure.

Secondary endpoints 11

1. -Sex -Age -Weight -Length -BMI -Body Surface Area (BSA) -Smoking status; including vaping and parental smoking status -Extra-intestinal manifestations -Comorbidity -Previous IBD medication -Co-medication - Renal function -MTX dose -Route of administration of MTX -Folic acid dose -Adherence
2. PBMC MTX-PG levels at 1,3,6 months (academic hospitals) and RBC MTX-PG levels at 1,3 and 6 months
3. -DNA SNP’s -FPGS activity -Transcriptome-wide RNA sequencing -Plasma cotinine (µg/L) -Erythrocyte folate (nmol/L) -Plasma homocysteine (µmol/L) -Plasma metabolomics
4. -Faecal microbiome -Faecal metabolome
5. - Drug survival due to treatment failure -Disease activity scores at baseline, 1,3,6 and 12 months -Faecal calprotectin at baseline, 1,3,6 and 12 months - CRP at baseline 1,3,6 and 12 months - SIBDQ at baseline, 1,3,6 and 12 months
6. - Drug survival; Defined as the cumulative incidence of MTX monotherapy discontinuation during the first year due to toxicity. -Whole blood count (CBC) at 1,3,6,12 months *routine -Liver blood test at 1,3,6,12 months *routine - MISS questionnaire at 1,3,6 and 12 months and if patients stop MTX treatment (tolerance defined as <6)
7. Clinical, genetic and metabolic determinants influencing MTX-PG concentrations and efficacy.
8. Clinical, genetic and metabolic determinants influencing MTX-PG concentrations and toxicity.
9. Infliximab dose - Route of administration of infliximab -Infliximab induction and maintenance schedule
10. Infliximab levels *routine
11. Anti-drug-antibodies to infliximab *routine

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Tim de Meij

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Tim de Meij

Locations

1 EU/EEA country · 2 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

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