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 attivo di grado da moderato a severo |
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E.1.1.1 | Medical condition in easily understood language |
Crohn's Disease |
Morbo di Crohn |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013099 |
E.1.2 | Term | Disease Crohns |
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 |
The primary objectives of Cohort A and B Induction Study are: • To evaluate the efficacy of filgotinib as compared to placebo in establishing clinical remission by Patient Reported Outcomes (PRO2) at Week 10 • To evaluate the efficacy of filgotinib as compared to placebo in establishing endoscopic response at Week 10
The primary objectives of the Maintenance Study are: • To evaluate the efficacy of filgotinib as compared to placebo in establishing clinical remission by PRO2 at Week 58 • To evaluate the efficacy of filgotinib as compared to placebo in establishing endoscopic response at Week 58 |
Gli obiettivi primari dello studio di induzione della coorte A e B sono: • Valutare l'efficacia di filgotinib rispetto al placebo nello stabilire la remissione clinica in base agli esiti riferiti dai pazienti (Patient-Reported Outcomes, PRO2) alla Settimana 10 • Valutare l'efficacia di filgotinib rispetto al placebo nello stabilire la risposta endoscopica alla Settimana 10
Gli obiettivi primari dello studio di mantenimento sono: • Valutare l'efficacia di filgotinib rispetto al placebo nello stabilire la remissione clinica in base al punteggio PRO2 alla Settimana 58 • Valutare l'efficacia di filgotinib rispetto al placebo nello stabilire la risposta endoscopica alla Settimana 58
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E.2.2 | Secondary objectives of the trial |
Key secondary objectives of both Cohort A Induction Study & Cohort B Induction Study are: • To evaluate the efficacy of filgotinib as compared to placebo in establishing clinical remission by Crohn's Disease Activity Index (CDAI) at Week 10 • To evaluate the efficacy of filgotinib as compared to placebo in establishing both clinical remission by PRO2 score & endoscopic response at Week 10 |
Gli obiettivi secondari chiave dello studio di induzione della coorte A, B e dello studio di mantenimento sono sono: • Valutare l'efficacia di filgotinib rispetto al placebo nello stabilire la remissione clinica in base all'indice di attività del morbo di Crohn (Crohn’s Disease Activity Index, CDAI) alla Settimana 10 • Valutare l'efficacia di filgotinib rispetto al placebo nello stabilire sia la remissione clinica in base al punteggio PRO2 che la risposta endoscopica (combinate in un unico endpoint a livello del paziente) alla Settimana 10
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenomics Version: Amendment 2 Date: 10/11/2016 Title: Genomic Substudy Objectives: An optional genomic substudy will be performed in all subjects who agree to participate and provide their additional specific consent. The genomic sample should be collected at the Day 1 visit, but may be collected at any time during the study.
Other types of substudies Specify title, date and version of each substudy with relative objectives: Pharmacokinetic (PK) Substudy
An optional PK substudy will be performed in a subset of subjects (approximately 30 subjects each in Cohort A and Cohort B) who provide a separate informed consent. In the PK substudy, the daily dose of study drug should be administered under supervision in the clinic (between Week 2 and Week 10 inclusive), and additional PK samples should be collected predose and at 0.5, 1, 2, 3, 4, and 6 hours post dose.
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Farmacogenomica Versione: Amendment 2 Data: 10/11/2016 Titolo: Sottostudio genomico Obiettivi: Un sottostudio genomico opzionale verrà eseguito per tutti i soggetti che accettano di partecipare e fornire il loro consenso specifico aggiuntivo. Il campione genomico dovrebbe essere raccolto alla visita del Giorno 1, ma potrebbe essere raccolto in qualsiasi momento durante lo studio.
Altre tipologie di sottostudi specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Sottostudio farmacocinetico (PK)
Un sottostudio PK opzionale verrà effettuato in un sottoinsieme di soggetti (circa 30 soggetti per ciascuna coorte A e B) che forniscono un consenso informato separato. Nel sottostudio PK, la dose quotidiana del farmaco dello studio dovrebbe essere somministrata sotto supervisione in ambulatorio (in occasione di una visita tra la Settimana 2 e la Settimana 10, incluse) e i campioni PK devono essere raccolti prima della somministrazione e alle ore 0.5, 1, 2, 3, 4 e 6 dopo la somministrazione.
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E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for participation in either the Cohort A or B Induction Study. • Must have the ability to understand and sign a written ICF, which must be obtained prior to initiation of study procedures • Males or non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the date of the screening visit • Females of childbearing potential must have a negative pregnancy test at screening and baseline • Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception • Documented diagnosis of CD with a minimum disease duration of 6 months with involvement of the ileum and/or colon at a minimum • Moderately or severely active CD • Meet one of the protocol specified tuberculosis (TB) screening criteria • May be receiving the following drugs (subjects on these therapies must be willing to remain on stable doses for the times noted in the protocol) - Oral 5-aminosalicylate (5-ASA) compounds - Azathioprine or 6-mercaptopurine (6-MP) or methotrexate (MTX) - Oral corticosteroid therapy - Antibiotics for the treatment of CD • Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose • Must be up to date on colorectal cancer screening and surveillance as standard of care according to local guidelines
Subjects must meet all of the additional inclusion criteria to be eligible for participation in Cohort A Induction Study. • Previously demonstrated an inadequate clinical response, loss of response to, or intolerance to at least one of the following agents (depending on current country treatment recommendations/guidelines): - Corticosteroids - Immunomodulators
Subjects must meet all of the additional inclusion criteria to be eligible for participation in Cohort B induction study. • Previously demonstrated an inadequate clinical response, loss of response to, or intolerance to at least one of the following agents (depending on current country treatment recommendations/guidelines): - TNFa Antagonists - Vedolizumab - Ustekinumab • Must not have used any TNFa antagonist or vedolizumab = 8 weeks prior to screening , ustekinumab IV or SC =12 weeks prior to screening, or any other biologic agent = 8 weeks prior to screening or within 5 times the half-life of the biologic agent prior to screening, whichever is longer
Subjects must meet all of the following inclusion criteria to be eligible for participation in the Maintenance Study. • Completion of Cohort A or B induction study with either clinical remission by PRO2 or endoscopic response at Week 10 • Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose • May be on oral corticosteroid therapy (prednisone prescribed at a stable dose = 30 mg/day or budesonide at a dose of = 9 mg/day); dose must remain stable to Week 14 |
Per un elenco completo dei criteri di inclusione ed esclusione dello studio, fare riferimento alla sezione 4 del protocollo. |
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E.4 | Principal exclusion criteria |
Refer to Protocol section 4 |
Per un elenco completo dei criteri di inclusione ed esclusione dello studio, fare riferimento alla sezione 4 del protocollo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Cohort A and B Induction Study • The proportion of subjects achieving clinical remission by PRO2 at Week 10 • The proportion of subjects achieving endoscopic response at Week 10
Maintenance Study • The proportion of subjects achieving clinical remission by PRO2 at Week 58 • The proportion of subjects achieving endoscopic response at Week 58 |
Studi di induzione (coorti A e B) • La percentuale di soggetti che ottiene la remissione clinica sostenuta in base al punteggio PRO2 alle Settimane 10 • La percentuale di soggetti che ottiene la risposta endoscopica alla Settimana 10
Studio di mantenimento • La percentuale di soggetti che ottiene la remissione clinica sostenuta in base al punteggio PRO2 alle Settimane 58 • La percentuale di soggetti che ottiene la risposta endoscopica alla Settimana 58 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 10 and Week 58 |
Settimana 10 e settimana 58 |
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E.5.2 | Secondary end point(s) |
Cohort A and B Induction Study The key secondary endpoints are: • The proportion of subjects achieving clinical remission by CDAI at Week 10 • The proportion of subjects achieving both clinical remission by PRO2 and endoscopic response (combined into a single endpoint on a patient level) at Week 10
Maintenance Study The key secondary endpoints are: • The proportion of subjects achieving clinical remission by CDAI at Week 58 • The proportion of subjects achieving sustained clinical remission by PRO2 at Weeks 10 and 58 • The proportion of subjects achieving both clinical remission by PRO2 and endoscopic response (combined into a single endpoint on a patient level) at Week 58 • The proportion of subjects achieving 6 month corticosteroid-free remission by PRO2 at Week 58 |
Studi di induzione (coorti A e B) • La percentuale di soggetti che ottiene la remissione clinica in base al punteggio CDAI alla Settimana 10 • La percentuale di soggetti che ottiene sia la remissione clinica in base al punteggio PRO2 che la risposta endoscopica (combinate in un unico endpoint a livello del paziente) alla Settimana 10
Studio di mantenimento: • La percentuale di soggetti che ottiene la remissione clinica in base al punteggio CDAI alla Settimana 58 • La percentuale di soggetti che ottiene la remissione clinica sostenuta in base al punteggio PRO2 alle Settimane 10 e 58 • La percentuale di soggetti che ottiene sia la remissione clinica in base al punteggio PRO2) che la risposta endoscopica (combinate in un unico endpoint a livello del paziente) alla Settimana 58 • La percentuale di soggetti che ottiene la remissione PRO2 senza corticosteroidi per 6 mesi alla Settimana 58
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 10 and Week 58 |
Settimana 10 e settimana 58 |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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) | 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 | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Disegno dello studio con fase combinata di induzione e mantenimento |
Combined induction and maintenance phase study design |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 180 |
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 |
Canada |
Georgia |
Hong Kong |
India |
Israel |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
New Zealand |
Russian Federation |
Serbia |
Singapore |
South Africa |
Taiwan |
Ukraine |
United States |
Austria |
Belgium |
Bulgaria |
Croatia |
France |
Germany |
Greece |
Iceland |
Italy |
Netherlands |
Norway |
Poland |
Portugal |
Romania |
Slovakia |
Spain |
Sweden |
Switzerland |
United Kingdom |
Czechia |
Argentina |
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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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End of Study is defined as when the last subject has completed 58 weeks of treatment plus 30 days follow-up. |
Per conclusione della sperimentazione si intende quando l'ultimo soggetto ha completato le 58 settimane di trattamento più 30 giorni di follow-up |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
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 | 30 |