Risk stratified randomized controlled trial in paediatric Crohn’s Disease: Methotrexate versus azathioprine or adalimumab for maintaining remission in patients at low or at high risk for aggressive disease course, respectively – a treatment strategy

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2016-000522-18-FR
• Date of registration: 21/06/2016
• Prospective Registration: Yes
• Primary sponsor: PIBDNet
• Public title: Risk stratified randomized controlled trial in paediatric Crohn’s Disease: Methotrexate versus azathioprine or adalimumab for maintaining remission in patients at low or at high risk for aggressive disease course, respectively – a treatment strategy
• Scientific title: Risk stratified randomized controlled trial in paediatric Crohn’s Disease: Methotrexate versus azathioprine or adalimumab for maintaining remission in patients at low or at high risk for aggressive disease course, respectively – a treatment strategy - REDUCE-RISKincd-PIBD-TRIAL
• Target sample size: 312
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000522-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: yes Other: yes Other trial design description: To ensure blinding of a 2nd physician who scores wPCDAI, PCDAI & PGA at each visit If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Belgium, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, United Kingdom

Contacts

• Name: Sandrine ROUX
• Affiliation: PIBDNet

• Name: Sandrine ROUX
• Affiliation: PIBDNet

Key inclusion & exclusion criteria

Inclusion criteria:
• Children 6-17, with a new-onset CD diagnosed using established criteria, only steroid-based or EN based induction therapies are allowed.
• Luminal active CD (B1) with or without B2 and/or B3 disease behavior
• Initial exposure to 5-ASA and derivate is tolerated
• Exposure to antibiotics is tolerated
• Informed and signed consent

Are the trial subjects under 18? yes
Number of subjects for this age range: 312
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Previous therapy with any IBD-related medications other than induction therapy as detailed in this protocol.
• Pregnancy or refusal to use contraceptives during the study period in pubertal patients (both boys and girls) unless absolute abstinence (no sexual activity) is confirmed at each study visit. Positive pregnancy testing throughout the study will trigger prompt withdrawal of the patient from the study.
• Children with perianal fistulising disease who require surgical therapy (drainage, seton placement)
• Patients homozygous for TPMT (or very low TPMT activity (<6 nmol/h/ml erythrocytes or <9nmol 6MTG/g Hb/h), unless they qualify as high risk patients
• Evidence of un-drained and un-controlled abscess/phlegmon
• Patients with inactive disease at screening (i.e. disease diagnosis) defined by wPCDAI=12.5 and normal CRP and ESR.
• Contraindication to any drugs used in the trial
• Current or previous malignancy
• Serious comorbidities interfering with drug therapy or interpretation of outcome parameters or will make it unlikely that the patients will finish the trial.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Crohn’s disease

Intervention(s)

Product Name: humira
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 160-

Product Name: Imurel
Pharmaceutical Form: Coated tablet
INN or Proposed INN: azathioprine
CAS Number: 446-86-6
Other descriptive name: AZATHIOPRINE
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 2.5-

Trade Name: Methotrexate
Product Name: methotrexate
Pharmaceutical Form: Solution for injection

Primary Outcome(s)

Primary end point(s): Comparing the two treatment arms per group
for sustained steroid/EN-free remission at Month 12, where sustained remission is defined as wPCDAI =12.5 and CRP =1,5-fold upper limit without a relapse or need for EEN/steroids since week 12.

Main Objective: To compare the effectiveness of weekly subcutaneously administered MTX for maintaining relapse-free sustained steroid/EN-free 1-year remission compared with:
• daily oral AZA/6MP in low risk paediatric CD
• subcutaneously administered adalimumab in high risk paediatric CD

Secondary Objective: Comparison between the two treatment arms per risk group (high risk or low risk for aggressive disease evolution) (and inter-risk group analysis for MTX-
treated patients)

Timepoint(s) of evaluation of this end point: At months 12

Secondary Outcome(s)

Secondary end point(s): Comparing the 2 treatment arms per risk group and comparing methotrexate treatment between high and low risk group

Timepoint(s) of evaluation of this end point: At months 12

Secondary ID(s)

2016-01

Source(s) of Monetary Support

PIBDNet