Pharmacokinetic Infliximab Data in Pediatric Crohn's Disease
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age1-15
SponsorErasmus Medical Center
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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)
Trial design
Design model
Single group
Treatments tested in this trial
Infliximab
DrugIFX 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.
Treatment groups
50 Participants
are divided into 1 treatment groupGroup A: Intensified induction scheme with InfliximabExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Proportion of patients with IFX Trough Levels ≥ 5 µg/mL at week 12 without treatment escalation
Treatment escalation is defined as any additional CD-related medication or IBD-related abdominal surgery
Time frame
12 weeksSecondary outcomes
1
Proportion of patients with IFX Trough Levels ≥ 5 µg/mL at week 24 without the need for treatment escalation
Treatment escalation is defined as any additional CD-related medication or IBD-related abdominal surgery
Time frame
24 weeks2
Clinical and biochemical remission at weeks 4, 12, and 24 without the need for treatment escalation in patients with TL ≥ 5 µg/mL and in patients with TL < 5 µg/mL.
Clinical remission is defined as wPCDAI \<12.5 Biochemical remission is defined as CRP \<5 mg/dL, FC \<250 ug/g.
Time frame
24 weeks3
Predictors of IFX Trough Levels at weeks 4, 12, and 24. Factors included in this analysis will be sex, age, body mass index (BMI), wPCDAI, IBD laboratory values, antibodies to Infliximab (ATI), dose, and interval of IFX infusions.
Time frame
24 weeks4
Development of antibodies to IFX until week 24
ATI's will be assessed if IFX TL is \<1 ug/ml at week 4, 12 or 24.
Time frame
24 weeksOther outcomes
1
Proportions of patients with primary non-response
Primary non-response: absence of response (wPCDAI decrease \> 17.5) at week 6 compared to baseline
Time frame
24 weeks2
Proportions of patients with secondary loss of response (LOR)
Secondary LOR: either an increase in wPCDAI \> 17.5 or a total wPCDAI score \> 40 in a patient who previously responded to induction treatment rates over time.
Time frame
24 weeks3
Evaluation of number of adverse events
Adverse event rate over time.Adverse events are defined as any undesirable experience occurring to a subject during the study, whether considered related to the investigational product or not. All adverse events reported spontaneously by the subject or observed by the investigator, or his staff will be recorded.
Time frame
24 weeks4
Complications rate
Complication rate (fistulas, abscesses, strictures, surgery, extraintestinal manifestations) over time.
Time frame
24 weeksSponsors and contacts
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Source ClinicalTrials.gov