E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Crohn's disease |
Ziekte van Crohn |
|
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 |
To determine the efficacy and safety of top-down IFX treatment in moderate-to-severe pediatric CD. |
Om de effectiviteit en veiligheid van top-down infliximab te bepalen in kinderen met matig-ernstige ziekte van Crohn |
|
E.2.2 | Secondary objectives of the trial |
Determination of pharmacokinetic/-dynamic profile of IFX and finding predictors of response to IFX in pediatric CD |
Nader bepalen van het farmacokinetisch en -dynamisch profiel van infliximab in kinderen met de ziekte van Crohn en om voorspellende markers van respons te identificeren |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosed with Crohn's disease Moderate-to-severe disease activity Aged 3-17 Untreated |
Gediagnosticeerd met de ziekte van Crohn Matig tot ernstige ziekteactiviteit Leeftijd 3-17 jaar Onbehandeld |
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E.4 | Principal exclusion criteria |
Need for surgery Severe comorbidity or severe infection Active perianal fistulas Pregnancy |
Operatie indicatie Ernstige comborbiditeit of ernstige infectie Active perianale fistels Zwangerschap |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical remission at 52 weeks without need for additional CD related therapy or surgery. |
Percentage van klinische remissie op 52 weken zonder dat aanvullende CD gerelateerde therapie is gebruikt of operaties zijn verricht. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints • Clinical response (decrease in wPCDAI >17.5) and remission (wPCDAI <12.5) rates at week 10 • Mucosal healing rates at week 10 assessed by endoscopy (absence of ulcers) and calprotectin (<100 µg/g), and at week 52 assessed by endoscopy (performed on a voluntary basis, or if clinically indicated) and/or calprotectin • Growth (change in height and BMI Z-scores, bone age and pubertal development) • Quality of life at week14 and 52 (IMPACT III) • Therapy failure rates over time (primary non-response, loss of response and medication intolerance) • Cumulative therapy use (steroids, immunomodulators, biologicals, etc)
Secondary safety endpoints • Adverse events rates • Complication rate at 52 weeks (fistulas, abscesses, strictures, surgery, extra-intestinal manifestations)
Long-term follow-up endpoints (5 years) • Yearly clinical remission rates without need for additional CD-related therapy or surgery • Yearly clinical response, clinical remission and mucosal healing rates • Number of flairs • Quality of life at 5 years • Cumulative therapy use (steroids, immunomodulators, biologicals, etc) • Adverse events rate • Complication rate (fistulas, abscesses, strictures, surgery, extra-intestinal manifestations)
Sub analyses • Correlation between clinical disease activity, fecal calprotectin and endoscopic disease severity • Comparing efficacy and safety endpoints between the two step-up treatment options (prednisolon+AZA vs EEN+AZA)
Additional objectives • Determination of PK/PD properties of IFX in children • Identification of predictive biomarkers of response to IFX • Comparing cost-efficacy of top-down versus step-up
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Secundaire effectiviteits uitkomstmaten • Klinische response en remissie percentages op week 10 • Mucosaal herstel op 10 weken en 52 weken, bepaald door endoscopie en/of calprotectine • Groei (toename in lengte en BMI Z-scores, botleeftijd en geslachtsrijping) • Toename in kwaliteit van leven op week 14 en 52 • Het voorkomen van therapie falen over tijd (primair non-response, verlies van response en falen vanwege medicatie bijwerkingen) • Cumulatief therapie gebruik (steroïden, immunomodulatoren, biologicals, etc)
Secondaire veiligheids uitkomstmaten • Bijwerkingen • Complicaties op 52 weken (fistels, abscessen, strictuur vorming, operaties, extra-intestinale manifestaties)
Lange-termijn uitkomstmaten (5 jaar) • Jaarlijkse klinische remissie percentage zonder dat aanvullende CD gerelateerde therapie is gebruikt of operaties zijn verricht. • Jaarlijkse klinische respons, remissie en mucosaal herstel percentages • Aantal ziekte opvlammingen • Kwaliteit van leven • Cumulatief therapie gebruik (steroïden, immunomodulatoren, biologicals, etc) • Bijwerkingen en complicaties (fistels, abscessen, strictuur vorming, operaties, extra-intestinale manifestaties)
Subanalyses • Relatie tussen klinische ziekte activiteit, calprotectine en endoscopische ziekte ernst • Vergelijken effectiviteit- en veiligheidsuitkomstmaten tussen de twee step-up behandelmethoden (prednisolon+AZA vs EEN+AZA)
Additioneel onderzoek • Bepalen van het farmacokinetisch profiel van infliximab in kinderen • Onderzoek naar voorspellende factoren voor respons op infliximab • Vergelijken van kost-effectiviteit van top-down versus step-up |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 10, 52 and/or 260 |
Week 10, 52 en/of 260 |
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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 | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 | 6 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 25 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 25 |