Pharmacokinetic Infliximab Data in Pediatric Crohn's Disease

• Status: Not yet recruiting
• Trial end date: 2024-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Erasmus Medical Center
• Treatments: Infliximab

Criteria

Inclusion Criteria:

• Anti-TNF-α naïve children (age 3-15 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

• Fistulizing/perianal disease at start of IFX treatment

• Severe comorbidity (not related to IBD)

• Patients who have already been exposed to anti-TNF-α

• Patients already started on biological treatment for another condition than 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