| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderately to Severely Active Crohn's Disease |
| Morbo di Crohn attivo da moderato a grave |
|
| E.1.1.1 | Medical condition in easily understood language |
| Inflammatory bowel disease (IBD) |
| Malattia infiammatoria intestinale (IBD) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10011401 |
| E.1.2 | Term | Crohn's disease |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
| 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 |
Phase 2 and Phase 3 Studies:
- To evaluate the clinical efficacy of guselkumab in participants with Crohn’s disease
- To evaluate the safety of guselkumab |
Studi di fase 2 e fase 3:
- Valutare l’efficacia clinica di guselkumab in partecipanti affetti dal morbo di Crohn
- Valutare la sicurezza di guselkumab
|
|
| E.2.2 | Secondary objectives of the trial |
Phase 2:
- To evaluate the dose-response of guselkumab to inform dose selection for the Phase 3 portion of this protocol
- To evaluate the efficacy of guselkumab on endoscopic improvement
- To evaluate the PK, immunogenicity, and pharmacodynamics (PD) of guselkumab therapy
Phase 3:
- To evaluate the efficacy of guselkumab on endoscopic improvement
- To evaluate the impact of guselkumab on HRQOL
- To evaluate the PK, immunogenicity, and PD of guselkumab therapy |
Fase 2:
- Valutare la risposta al dosaggio di guselkumab, al fine di raccogliere informazioni per la selezione della dose per la fase 3 del protocollo
- Valutare l’efficacia di guselkumab sul miglioramento endoscopico
- Valutare la PK, l’immunogenicità e la farmacodinamica (PD) della terapia con guselkumab
Fase 3:
- Valutare l’efficacia di guselkumab sul miglioramento endoscopico
- Valutare l’impatto di guselkumab sulla HRQOL
- Valutare la PK, l’immunogenicità e la PD della terapia con guselkumab |
|
| 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: -
Date: 06/12/2017
Title: Phase 2 and 3 study. Optional pharmacogenomic sub-study
Objectives: Collect DNA to allow for the identification of genetic factors that may influence the PK, PD, efficacy, safety, or tolerability of guselkumab and to identify genetic factors associated with Crohn's disease or the response to guselkumab or ustekinumab treatment.
Other types of substudies
Specify title, date and version of each substudy with relative objectives: Phase 2 and 3 study. Optional Week 4 ileocolonoscopy sub-study: Exploratory analyses of intestinal mucosal tissue obtained by biopsy at Week 4 will be performed
to delineate the mechanisms of action of guselkumab and ustekinumab.
|
Farmacogenomica
Versione: -
Data: 06/12/2017
Titolo: Studio di fase 2 e 3. Sottostudio facoltativo sulla farmacogenomica
Obiettivi: Raccolta del DNA per consentire l’identificazione dei fattori genetici che possono influenzare PK, PD, efficacia, sicurezza o tollerabilità di guselkumab e identificare i fattori genetici associati al morbo di Crohn o la risposta al trattamento con guselkumab o ustekinumab.
Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Studio di fase 2 e 3. Sottostudio facoltativo con ileocolonscopia alla Settimana 4: verranno condotte analisi esplorative della mucosa intestinale acquisita tramite biopsia alla Settimana 4 allo scopo di determinare i meccanismi d’azione di guselkumab e ustekinumab
|
|
| E.3 | Principal inclusion criteria |
- Have Crohn's disease (CD) or fistulizing Crohn's disease of at least 3 months duration (defined as a minimum of 12 weeks), with colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology, and/or endoscopy
- Have moderate to severe CD as assessed by CDAI, stool frequency (SF), and abdominal pain (AP) scores, and Simple Endoscopic Score for
Crohn's Disease (SES-CD)
- Have screening laboratory test results within the protocol specified parameters
- A female participant of childbearing potential must have a negative urine pregnancy test result at screening and baseline
- Demonstrated intolerance or inadequate response to conventional or to biologic therapy for CD |
- Presenza di morbo di Crohn (MC) o morbo di Crohn fistolizzante da almeno 3 mesi (definito come un minimo di 12 settimane), con colite, ileite o ileocolite, confermato in ogni momento nel passato da una radiografia, istologia e/o endoscopia
- Presenza di MC da moderata a grave secondo il CDAI, frequenza delle feci (SF) e punteggi relativi al dolore addominale (AP) e Simple Endoscopic Score for Crohn’s Disease (SES-CD)
- Risultati di laboratorio allo screening nei parametri specificati dal protocollo
- Le partecipanti potenzialmente fertili devono avere un risultato per il test delle urine sulla gravidanza negativo allo screening e al baseline
- Intolleranza dimostrata o risposta inadeguata alla terapia convenzionale o biologica per MC |
|
| E.4 | Principal exclusion criteria |
- Current diagnosis of ulcerative colitis or indeterminate colitis
- Has complications of Crohn's disease, such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation
- Unstable doses of concomitant Crohn's disease therapy
- Receipt of Crohn's disease approved biologic agents, investigational agents, or procedures outside of permitted timeframe as specified in the protocol
- Prior exposure to p40 inhibitors or p19 inhibitors
- Any medical contraindications preventing study participation |
- Attuale diagnosi di colite ulcerante o colite indeterminata
- Presenza di complicazioni della MC, come strozzature o stenosi, sindrome dell’intestino corto, o qualsiasi altra manifestazione
- Dosi instabili di terapia concomitante del morbo di Crohn
- Assunzione di agenti biologici approvati per il morbo di Crohn, agenti sperimentali, o procedure estranee dal quadro permesso specificato nel protocollo
- Precedente esposizione agli inibitori p40 o agli inibitori p19
- Qualsiasi controindicazione medica che impedisca la partecipazione allo studio |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Phase 2: Change from Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 12
Phase 3: Clinical remission at week 12 (defined as CDAI score <150) |
Fase 2: Variazione dal basale nel punteggio CDAI alla Settimana 12
Fase 3: Remissione clinica alla Settimana 12 (definita come punteggio CDAI <150) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Phase 2:
- Clinical remission at Week 12 (defined as CDAI score <150)
- Clinical response at Week 12 (defined as =100-point reduction from baseline in CDAI score or CDAI score <150)
- PRO-2 remission at Week 12 (defined based on average daily stool frequency (SF) and average daily abdominal pain (AP) score)
- Clinical-biomarker response at Week 12 (clinical response based on CDAI score and reduction from baseline in CRP or fecal calprotectin)
- Endoscopic response at Week 12 (measured by the Simple Endoscopic Score for Crohn's
Disease (SES-CD). The SES-CD is based on the evaluation of 4 endoscopic components across 5 ileocolonic segments, with a total score ranging from 0 to 56.)
Phase 3:
- Clinical remission at Week 48 (defined as CDAI < 150)
- Durable clinical remission at Week 48 (defined as CDAI<150 for the majority of visits between Week 12 and Week 48.)
- Corticosteroid-free clinical remission at Week 48 (defined as CDAI score <150 at Week 48 and not receiving corticosteroids at Week 48)
- PRO-2 remission at Week 12 and 48 (based on average daily stool frequency (SF) and average daily abdominal pain (AP) score)
- Endoscopic response at Week 12 and 48 (measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD))
• Fatigue response at Week 12 (based on the PROMIS Fatigue Short Form 7a) |
Fase 2:
- Remissione clinica alla Settimana 12 (definita come punteggio CDAI <150)
- Risposta clinica alla Settimana 12 (definita come riduzione di =100 punti dal basale nel punteggio CDAI oppure punteggio CDAI <150)
- Remissione PRO-2 alla Settimana 12 (definita sulla base della media della frequenza delle feci giornaliera (SF) e del punteggio giornaliero medio del dolore addominale (AP))
- Risposta dei biomarcatori clinici alla Settimana 12 (risposta clinica basata sul punteggio CDAI e su una riduzione dal basale della CRP o della calprotectina fecale)
- Risposta endoscopica alla Settimana 12 (misurata dal Simple Endoscopic Score for Crohn’s Disease (SES-CD)). Il SES-CD si basa sulla valutazione dei 4 componenti endoscopici attraverso 5 segmenti ileocolonici, con un punteggio totale che varia da 0 a 56)
Fase 3:
- Remissione clinica alla Settimana 48 (definita come punteggio CDAI <150)
- Remissione clinica duratura alla Settimana 48 (definita come punteggio CDAI <150 per la maggior parte delle visite tra la Settimana 12 e la Settimana 48)
- Remissione clinica libera da corticosteroidi alla Settimana 48 (definita come punteggio CDAI <150 alla Settimana 48 e nessuna somministrazione di corticosteroidi alla Settimana 48)
- Remissione PRO-2 alla Settimana 12 e 48 (basata sulla media della frequenza delle feci giornaliera (SF) e del punteggio giornaliero medio del dolore addominale (AP))
- Risposta endoscopica alla Settimana 12 e 48 (misurata dal Simple Endoscopic Score for Crohn’s Disease (SES-CD))
• Risposta all’affaticamento alla Settimana 12 (basata sul Modulo breve sull’affaticamento PROMIS 7a |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| week 12 or 48 as listed above |
| settimana 12 o 48 come elencato sopra |
|
| 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 | Yes |
| 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 | Yes |
| 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) | Yes |
| 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 | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 9 |
| 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 | 14 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 121 |
| 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 |
| Belarus |
| Bosnia and Herzegovina |
| Brazil |
| Canada |
| China |
| Colombia |
| Georgia |
| Israel |
| Japan |
| Jordan |
| Korea, Republic of |
| Lebanon |
| North Macedonia |
| New Zealand |
| Russian Federation |
| Saudi Arabia |
| Serbia |
| South Africa |
| Taiwan |
| Tunisia |
| Turkey |
| Ukraine |
| United States |
| Austria |
| Belgium |
| Croatia |
| Czechia |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Latvia |
| Lithuania |
| Netherlands |
| Poland |
| Portugal |
| Slovakia |
| Spain |
| United Kingdom |
|
| 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
|
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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