E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Crohn's disease |
Ziekte van Crohn |
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E.1.1.1 | Medical condition in easily understood language |
Crohn's disease |
Ziekte van Crohn |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 (=therapeutic trough levels) without treatment escalation in pediatric CD patients. |
Het doel van de PRO-RAPID (Prospectieve Analyse Pharmacokinetiek Inflammatoire Darmziekten) studie is om te onderzoeken of een intensiever infliximabbehandelschema leidt tot betere uitkomsten van de ziekte. |
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E.2.2 | Secondary objectives of the trial |
• Proportion of patients with IFX TL ≥ 5 μg/mL at week 24 without the need for treatment escalation • 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 • Predictors of IFX TLs at weeks 4, 12, and 24. Factors included in this analysis will be sex, age, body mass index (BMI), wPCDAI, IBD laboratory values, ATI, dose, and interval of IFX infusions • Development of ATI until week 24 • Prediction of patients who will respond vs. those who will not despite adequate TLs at weeks 12 and 24 based on proteomics analysis by OLINK • Evaluation of quality of life at baseline, weeks 4, 12, and 24 in all patients • Adverse event rate over time |
• Percentage patienten met IFX spiegels ≥ 5 μg/mL op week 24 zonder behandelintensificatie. • Klinische en biochemische remissie op week 4, 12 en 24 zonder behandelintensificatie bij patienten met IFX spiegel≥ 5 μg/m en patienten met IFX spiegel < 5 μg/mL. • Voorspellende factoren van IFX spiegels op week 4, 12 en 24. Covariaten die worden meegenomen in deze analyse zijn geslacht, XML File Identifier: PcjOirbzROKqle83AVOY7ncmP7o= Page 10/20 leeftijd, body mass index (BM), wPCDAI, IBD lab, antistoffen tegen infliximab and dosering en interval van infliximab infusen. • Ontwikkeling van antistoffen tegen infliximab tot en met week 24. • Onderzoek naar voorspellende eiwitten (gebaseerd op OLINK analyse) op patienten die reageren vs niet reageren op behandeling met inflximab ondanks adequate infliximab spiegels • Kwaliteit van leven op baseline, week 12 en |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 [11]. 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. |
-Kinderen (1-15 jaar) -Geen eerdere behandeling met anti-TNF -Indicatie tot starten anti-TNF volgens ECCO-ESPGHAN richtlijn |
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E.4 | Principal exclusion criteria |
Patients with the following characteristics will be excluded: - 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 |
Patiënten met de volgende kenmerken zullen worden geexcludeerd: Bevestigde monogenetische IBD Diagnose van UC of IBD-U, ulceratieve colitis like Actieve fistelvormende/perianale ziekte bij aanvang van IFX-behandeling (patiënten met inactieve fistelvormende/perianale ziekte mogen deelnemen) Ernstige comorbiditeit (niet gerelateerd aan IBD) Onmiddellijke behoefte aan chirurgie (bijvoorbeeld symptomatische stenose of vernauwing in de darm) Ernstige infectie zoals sepsis of opportunistische infecties, positieve tuberculinetest of een thoraxfoto die consistent is met tuberculose of maligniteit Zwangerschap, vermoedelijk of definitief Behandeling met anti-TNF of andere biologische geneesmiddelen in het verleden Start van corticosteroïden of mesalazine minder dan 2 weken voorafgaand aan de eerste IFX-infusie Start van exclusieve enterale voeding minder dan 2 weken voorafgaand aan de eerste IFX-infusie
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients with IFX TL ≥ 5 μg/mL at week 12 without treatment escalation. |
Percentage patienten met IFX spiegels ≥ 5 μg/mL op week 12 zonder behandelintensificatie. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Proportion of patients with IFX TL ≥ 5 μg/mL at week 24 without the need for treatment escalation • 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 • Predictors of IFX TLs at weeks 4, 12, and 24. Factors included in this analysis will be sex, age, body mass index (BMI), wPCDAI, IBD laboratory values, ATI, dose, and interval of IFX infusions • Development of ATI until week 24 • Prediction of patients who will respond vs. those who will not despite adequate TLs at weeks 12 and 24 based on proteomics analysis by OLINK • Evaluation of quality of life at baseline, weeks 4, 12, and 24 in all patients • Adverse event rate over time |
• Percentage patienten met IFX spiegels ≥ 5 μg/mL op week 24 zonder behandelintensificatie. • Klinische en biochemische remissie op week 4, 12 en 24 zonder behandelintensificatie bij patienten met IFX spiegel≥ 5 μg/m en patienten met IFX spiegel < 5 μg/mL. • Voorspellende factoren van IFX spiegels op week 4, 12 en 24. Covariaten die worden meegenomen in deze analyse zijn geslacht, leeftijd, body mass index (BM), wPCDAI, IBD lab, antistoffen tegen infliximab and dosering en interval van infliximab infusen. • Ontwikkeling van antistoffen tegen infliximab tot en met week 24. • Onderzoek naar voorspellende eiwitten (gebaseerd op OLINK analyse) op patienten die reageren vs niet reageren op behandeling met inflximab ondanks adequate infliximab spiegels • Kwaliteit van leven op baseline, week 12 en 24. • Aantal bijwerkingen tot en met 24 weken |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
See within description of secondary endpoints |
Zie beschrijving van secundaire uitkomsten |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 24 |