RECRUITINGPhase 4INTERVENTIONAL

Pharmacokinetic Infliximab Data in Pediatric Crohn's Disease

Prospective Analysis of Pharmacokinetic Infliximab Data in Pediatric CD Patients (ProRAPID)

About This Trial

Rationale: Crohn's disease (CD) is a chronic, debilitating inflammatory bowel disease (IBD) which is diagnosed during childhood in up to one in ten patients. The use of anti-tumor necrosis factor (TNF)-α agents has significantly ameliorated CD management. Infliximab (IFX) is the first anti-TNF-α agent registered for pediatric CD. The current dosing recommendation of IFX is extrapolated from adult studies, and it is a weight-based dose (5 mg/kg) delivered during induction (infusion at weeks 0, 2, and 6) and maintenance (every 8 weeks). However, pediatric patients have a 25-40% lower drug exposure compared to adults, particularly children under 10 years of age, resulting in diminished efficacy and an increased risk of developing a complicated disease course. The investigators hypothesize that an intensified IFX induction scheme (instead of the current dosing recommendation) is more effective in the treatment of pediatric CD patients. Objective: The primary study objective of our study is to assess the efficacy of an IFX intensified induction scheme vs. a standard dosing schedule in improving drug exposure without treatment escalation in pediatric CD patients. Secondary objectives are clinical and biochemical remission without treatment escalation, development of antibodies to IFX (ATI) and adverse reactions. Study design: An international, multicenter, prospective, open-label trial. Study population: Anti-TNF-α naïve children (age 1-15 years) with CD and an indication to start IFX treatment. Intervention: IFX will be given intravenously at 10 mg/kg at week 0, and 5 mg/kg at weeks 2, 4, and 8 to all patients (induction). Maintenance will start at week 12, and then ideally continue every 6 weeks till week 24 (end of study). IFX trough levels will be measured at weeks 4, 12, and 24. During the maintenance, the IFX dose and/or interval adjustments, the IFX discontinuation or the start of a co-medication (i.e., an immunomodulator) will be possible on indication (i.e., primary nonresponse, secondary loss of response, intolerance to study medication) at the physicians' discretion. Follow-up will continue for the duration of the study (week 24). Main endpoint: Proportion of patients with IFX TL ≥ 5 µg/mL at week 12 without treatment escalation.

Who May Be Eligible (Plain English)

Who May Qualify: - Anti-TNF-α naïve children (age 1-15 years) with CD and an indication to start IFX treatment will be eligible for inclusion after a diagnosis of CD is made based on the Porto criteria. Indications of starting IFX treatment as per ECCO-ESPGHAN guidelines include non-response after induction with exclusive enteral nutrition or steroids, non-response to immunomodulators, severe growth delay, extensive disease and/or structuring or penetrating disease, with or without perianal disease. Evaluation of the indication to start IFX is performed at the discretion of the attending physician. Who Should NOT Join This Trial: - Established monogenetic IBD - Diagnosis with UC or IBD-U, ulcerative colitis like - Active fistulizing/perianal disease at start of IFX treatment (patients with inactive fistulizing/perianal disease are allowed to participate) - Severe comorbidity (not related to IBD) - Immediate need for surgery (i.e., symptomatic stenosis or stricture in the bowel) - Severe infection such as sepsis or opportunistic infections, positive tuberculin test or a chest radiograph consistent with tuberculosis or malignancy - Pregnancy, suspected or definitive - Treatment with anti-TNF or other biological drugs in the past - Start of corticosteroids or mesalazine less than 2 weeks prior to first IFX infusion - Start of Exclusive Enteral Nutrition less than 2 week prior to first IFX infusion Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Anti-TNF-α naïve children (age 1-15 years) with CD and an indication to start IFX treatment will be eligible for inclusion after a diagnosis of CD is made based on the Porto criteria. Indications of starting IFX treatment as per ECCO-ESPGHAN guidelines include non-response after induction with exclusive enteral nutrition or steroids, non-response to immunomodulators, severe growth delay, extensive disease and/or structuring or penetrating disease, with or without perianal disease. Evaluation of the indication to start IFX is performed at the discretion of the attending physician. Exclusion Criteria: * Established monogenetic IBD * Diagnosis with UC or IBD-U, ulcerative colitis like * Active fistulizing/perianal disease at start of IFX treatment (patients with inactive fistulizing/perianal disease are allowed to participate) * Severe comorbidity (not related to IBD) * Immediate need for surgery (i.e., symptomatic stenosis or stricture in the bowel) * Severe infection such as sepsis or opportunistic infections, positive tuberculin test or a chest radiograph consistent with tuberculosis or malignancy * Pregnancy, suspected or definitive * Treatment with anti-TNF or other biological drugs in the past * Start of corticosteroids or mesalazine less than 2 weeks prior to first IFX infusion * Start of Exclusive Enteral Nutrition less than 2 week prior to first IFX infusion

Treatments Being Tested

DRUG

Infliximab

IFX will be given intravenously at 10 mg/kg at week 0, and 5 mg/kg at weeks 2, 4, and 8 to all patients (induction). Maintenance will start at week 12, and then ideally continue every 6 weeks till week 24 (end of study). IFX trough levels will be measured at weeks 4, 12, and 24. During the maintenance, the IFX dose and/or interval adjustments, the IFX discontinuation or the start of a co-medication (i.e., an immunomodulator) will be possible on indication (i.e., primary nonresponse, secondary loss of response, intolerance to study medication) at the physicians' discretion.

Locations (1)

Erasmus Medical Center

Rotterdam, Netherlands