Pharmacokinetic Infliximab Data in Pediatric Crohn's Disease
Status:
Not yet recruiting
Trial end date:
2024-11-01
Target enrollment:
Participant gender:
Summary
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 3-15 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.