E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to severely active Crohn's disease (CD) |
Morbo di Crohn da moderatamente a gravemente attivo |
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E.1.1.1 | Medical condition in easily understood language |
Moderately to severely active Crohn's disease. Crohn's disease is a disease that causes inflammation of the digestive system. |
Morbo di Crohn da moderatamente a gravemente attivo. Il Morbo di Crohn è una malattia che causa infiammazione all'apparato digerente. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058815 |
E.1.2 | Term | Crohn's disease acute episode |
E.1.2 | System Organ Class | 100000004856 |
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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 evaluate the efficacy of 2 different dose regimens of vedolizumab IV in pediatric subjects with moderately to severely active CD during maintenance therapy, based on clinical and endoscopic assessments at Week 54. |
Valutare l’efficacia di 2 diversi regimi di dosaggio di vedolizumab per via endovenosa in soggetti pediatrici con MC da moderatamente a gravemente attivo durante la terapia di mantenimento, in base alle valutazioni cliniche ed endoscopiche alla Settimana 54. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of high and low doses of vedolizumab IV as measured by clinical and endoscopic remission at Weeks 14 and 54. • To evaluate the effect of high and low doses of vedolizumab IV in each weight group on achieving corticosteroid-free remission at Week 54. • To evaluate the effect of vedolizumab IV in each weight group on clinical response and clinical remission over time up to Week 54. • To characterize the exposure of 2 different dose regimens of vedolizumab in pediatric subjects with moderately to severely active CD after IV administration. • To evaluate safety in pediatric subjects on maintenance therapy up to Week 54. • To evaluate the immunogenicity of vedolizumab in pediatric subjects with moderately to severely active CD treated with vedolizumab IV. • To evaluate the effect of vedolizumab on patterns of growth and pubertal development in pediatric subjects with moderately to severely active CD during their participation in the study. |
Fare riferimento alla Sinossi in Italiano |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects male or female aged 2 to 17 years, inclusive, who weigh =10 kg at the time of screening and enrollment into the study. 2. Subjects with moderately to severely active CD diagnosed at least 1 month before screening, defined by a PCDAI >30 and an SES-CD >6 (oran SES-CD =4 if disease is confined to terminal ileum). 3. Subjects who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (eg, AZA, 6-mercaptopurine, methotrexate), and/or TNF-a antagonist therapy (eg, infliximab, adalimumab). This includes subjects who are dependent on corticosteroids or exclusive or partial enteral nutrition to control symptoms and who are experiencing worsening of disease in the moderate-to-severe range when attempting to wean off corticosteroids or discontinue exclusive enteral nutrition. 4. Subjects with extensive colitis or pancolitis of >8 years' duration or left-sided colitis of >12 years' duration must have documented evidence of a negative surveillance colonoscopy within 12 months before screening. 5. Subjects with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines. |
Soggetti ambosesso di età compresa tra 2 e 17 anni, inclusi, che pesano =10 kg al momento dello screening e dell’arruolamento nello studio. Soggetti con MC da moderatamente a gravemente attivo diagnosticato almeno 1 mese prima dello screening, definito da un PCDAI >30 e un SES-CD >6 (o un SES-CD =4 se la malattia è limitata all’ileo terminale). Soggetti che non hanno risposto, hanno perso la risposta o sono risultati intolleranti al trattamento con almeno 1 dei seguenti agenti: corticosteroidi, immunomodulatori (per es. AZA, 6-mercaptopurina, metotrexato) e/o terapia con antagonisti del TNF-a (per es. infliximab, adalimumab). Ciò include i soggetti che sono dipendenti da corticosteroidi o dalla nutrizione enterale esclusiva o parziale per il controllo dei sintomi e che manifestano un peggioramento della malattia nell’intervallo da moderato a grave quando tentano di sospendere i corticosteroidi o interrompere la nutrizione enterale esclusiva. I soggetti con colite estensiva o pancolite di durata >8 anni o colite al lato sinistro di durata >12 anni devono presentare evidenza documentata di una colonscopia di sorveglianza negativa entro 12 mesi prima dello screening. Soggetti con vaccinazioni che risultano aggiornate in base al programma vaccinale dell’infanzia accettato a livello nazionale. |
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E.4 | Principal exclusion criteria |
1. Subjects who have had previous exposure to approved or investigational anti-integrins, including but not limited to natalizumab, efalizumab, etrolizumab, or AMG 181, or mucosal addressin cell adhesion molecule-1 (MAdCAM-1) antagonists or rituximab. 2. Subjects who have had prior exposure to vedolizumab. 3. Subjects with hypersensitivity or allergies to any of the vedolizumab excipients. 4. Subjects who have received either (1) an investigational biologic (other than those listed in Exclusion Criterion #1) within 60 days or 5 half-lives before screening (whichever is longer); or (2) an approved biologic or biosimilar agent within 2 weeks before the first dose of study drug or at any time during the screening period. 5. Subjects with active cerebral/meningeal disease, signs/symptoms or history of progressive multifocal leukoencephalopathy (PML) or any other major neurological disorders including stroke, multiple sclerosis, brain tumor or neurodegenerative disease. 6. Subjects who currently require surgical intervention or are anticipated to require surgical intervention for CD during this study. 7. Subjects who have had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, known fixed stenosis of the intestine, short bowel syndrome, or >3 small intestine resections. 8. Subjects with a current diagnosis of indeterminate colitis. 9. Subjects with clinical features suggesting monogenic very early-onset inflammatory bowel disease. |
Soggetti che hanno avuto una precedente esposizione ad anti-integrine approvate o sperimentali, tra cui, a titolo esemplificativo ma non esaustivo, natalizumab, efalizumab, etrolizumab o AMG 181, o antagonisti della molecola di adesione cellulare addressina mucosale 1 (Mucosal Addressin Cell Adhesion Molecule-1, [MAdCAM-1]) o rituximab. Soggetti che sono stati precedentemente esposti a vedolizumab. Soggetti con ipersensibilità o allergie a uno qualsiasi degli eccipienti di vedolizumab. Soggetti che hanno ricevuto (1) un farmaco biologico sperimentale (diverso da quelli elencati nel Criterio di esclusione n. 1) entro 60 giorni o 5 emivite prima dello screening (a seconda di quale periodo sia più lungo); o (2) un agente biologico o biosimilare approvato nelle 2 settimane che precedono la prima dose del farmaco dello studio o in qualsiasi momento durante il periodo di screening. Soggetti con malattia cerebrale/meningea attiva, segni/sintomi o anamnesi di leucoencefalopatia multifocale progressiva (LMP) o eventuali altri disturbi neurologici maggiori, tra cui ictus, sclerosi multipla, tumore cerebrale o malattia neurodegenerativa. Soggetti con necessità attuale o prevista di ricorrere a un intervento chirurgico per l’MC durante questo studio. Soggetti che si sono sottoposti a colectomia subtotale o totale, si sottopongono a digiunostomia, ileostomia, colostomia o sono portatori di tasca ileo-anale, stenosi fissa nota dell’intestino, con sindrome dell’intestino corto o >3 resezioni dell’intestino tenue. Soggetti con diagnosi attuale di colite indeterminata. Soggetti con caratteristiche cliniche che suggeriscono la presenza di una malattia infiammatoria intestinale monogenica a insorgenza molto precoce. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Coprimary 1 (based on PCDAI): Clinical remission defined as a PCDAI =10 at Week 54. • Coprimary 2 (based on SES-CD): Endoscopic response at Week 54, where a subject achieves endoscopic response if he or she has a 50% reduction in SES-CD score from baseline. |
Co-primario 1 (basato sul PCDAI): remissione clinica definita come un PCDAI =10 alla Settimana 54. Co-primario 2 (basato sul SES-CD): risposta endoscopica alla Settimana 54, dove un soggetto raggiunge la risposta endoscopica se presenta una riduzione del 50% nel punteggio SES-CD rispetto al basale. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The end of study is defined as the Week 54 study visit. |
The end of study is defined as the Week 54 study visit. |
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E.5.2 | Secondary end point(s) |
• Clinical and endoscopic remission at Week 14, where a subject achieves both clinical and endoscopic remission if he or she meets the following definition: PCDAI =10 and SES-CD =4 with at least a 2-point reduction from baseline and no subscore >1. • Clinical and endoscopic remission at Week 54, where a subject achieves clinical and endoscopic remission if he or she meets the following definition: PCDAI =10 and SES-CD =4 with at least a 2-point reduction from baseline and no subscore >1. • Sustained clinical and endoscopic remission at Week 54, where a subject achieves sustained clinical and endoscopic remission if he or she achieved clinical and endoscopic remission (based on PCDAI and SESCD) at Week 14 and at Week 54. • Corticosteroid-free remission at Week 54, where a subject achieves corticosteroid-free clinical remission based on PCDAI at Week 54 and he or she has been off corticosteroids at least 12 weeks prior to Week 54. • Sustained endoscopic remission, where a subject achieves sustained endoscopic remission if he or she meets the following definition: SES-CD =4 with at least a 2 point reduction from baseline and no subscore >1, achieved at both Weeks 14 and 54. • Sustained clinical remission at Week 54, where a subject achieves sustained clinical remission if he or she achieved clinical remission (based on PCDAI) at Week 14 and at Week 54. • Serum trough concentrations of vedolizumab over time. • Positive antivedolizumab antibodies and positive neutralizing antivedolizumab antibodies during the study. • Sustained clinical response of subjects at Weeks 14 and 54, where a subject meets clinical response of if he or she has a PCDAI score <30 and reduction of the PCDAI by =15 points from baseline. • Clinical remission at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 where a subject achieves clinical remission if he or she meets the following definition: PCDAI =10. • Clinical response at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 where a subject achieves clinical response if he or she meets the following definition: PCDAI <30 with reduction in the PCDAI of =15 points from baseline. • Safety assessments: Descriptions of adverse events (AEs); serious adverse events (SAEs) and AEs of special interest (AESIs), including evaluation of opportunistic infection, such as PML, and liver injury, malignancies, infusion-related reactions, and hypersensitivity. • Change from baseline in weight gain and linear growth z-score during the course of dosing with vedolizumab. • Tanner Stage V at Week 54, where a subject achieves Tanner Stage V at Week 54 based on progression of pubertal changes from baseline. |
Remissione clinica ed endoscopica alla Settimana 14, dove un soggetto raggiunge sia la remissione clinica che endoscopica se soddisfa la seguente definizione: PCDAI =10; e SES-CD =4 con una riduzione di almeno 2 punti rispetto al basale e nessun sottopunteggio >1. Remissione clinica ed endoscopica alla Settimana 54, dove un soggetto raggiunge la remissione clinica ed endoscopica se soddisfa la seguente definizione: PCDAI =10; e SES-CD =4 con una riduzione di almeno 2 punti rispetto al basale e nessun sottopunteggio >1. Remissione clinica ed endoscopica sostenuta alla Settimana 54, dove un soggetto raggiunge la remissione clinica ed endoscopica sostenuta se ha raggiunto la remissione clinica ed endoscopica (in base al PCDAI e al SES-CD) alla Settimana 14 e alla Settimana 54. Remissione libera da corticosteroidi alla Settimana 54, dove un soggetto raggiunge la remissione clinica libera da corticosteroidi in base al PCDAI alla Settimana 54 e non ha assunto corticosteroidi per almeno 12 settimane prima della Settimana 54. Remissione endoscopica sostenuta, dove un soggetto raggiunge la remissione endoscopica sostenuta se soddisfa la seguente definizione: SES-CD =4 con una riduzione di almeno 2 punti rispetto al basale e nessun sottopunteggio >1, raggiunta alle Settimane 14 e 54. Remissione clinica sostenuta alla Settimana 54, dove un soggetto raggiunge la remissione clinica sostenuta se ha raggiunto la remissione clinica (in base al PCDAI) alla Settimana 14 e alla Settimana 54. Concentrazioni sieriche di valle di vedolizumab nel tempo. Anticorpi anti-vedolizumab positivi e anticorpi neutralizzanti anti-vedolizumab positivi durante lo studio. Risposta clinica sostenuta dei soggetti alle Settimane 14 e 54, dove un soggetto soddisfa la risposta clinica se presenta un punteggio PCDAI <30 e una riduzione del PCDAI di =15 punti rispetto al basale. Remissione clinica alle Settimane 2, 6, 10, 14, 22, 30, 38, 46 e 54, dove un soggetto raggiunge la remissione clinica se soddisfa la seguente definizione: un PCDAI =10. Risposta clinica alle Settimane 2, 6, 10, 14, 22, 30, 38, 46 e 54, dove un soggetto raggiunge la risposta clinica se soddisfa la seguente definizione: un PCDAI <30 con riduzione del PCDAI di =15 punti rispetto al basale. Valutazioni di sicurezza: descrizioni di eventi avversi (EA), eventi avversi seri (Serious Adverse Event, [SAE]) ed EA di particolare interesse (Adverse Events of Special Interest, [AESI]), compresa la valutazione delle infezioni opportunistiche, come LMP e lesione epatica, neoplasie maligne, reazioni correlate all’infusione e ipersensibilità. Variazione rispetto al basale nell’aumento di peso e nel punteggio z della crescita lineare nel corso della somministrazione di vedolizumab. Stadio V di Tanner alla Settimana 54, dove un soggetto raggiunge lo Stadio V di Tanner alla Settimana 54 in base alla progressione delle variazioni puberali rispetto al basale. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity |
Immunogenicity |
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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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Different doses of IMP are used in treatment arms |
Different doses of IMP are used in treatment arms |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Bosnia and Herzegovina |
Canada |
China |
Israel |
Japan |
New Zealand |
Russian Federation |
Ukraine |
United States |
Austria |
Belgium |
Croatia |
France |
Germany |
Hungary |
Italy |
Lithuania |
Poland |
Romania |
Slovakia |
Spain |
United Kingdom |
Czechia |
Greece |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The end of study is defined as the Week 54 study visit. |
The end of study is defined as the Week 54 study visit. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 15 |