E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Crohn's Disease |
maladie de Crohn active d’intensité modérée à sévère |
|
E.1.1.1 | Medical condition in easily understood language |
Inflammatory bowel disease (IBD) |
Maladie inflammatoire de l'intestin (MII) |
|
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 |
Etudes de phase 2 et 3:
-Évaluer l’efficacité clinique du guselkumab chez des participants atteints de la maladie de Crohn
− Évaluer la sécurité d’emploi du 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 pharmacokinetics (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 |
Phase 2:
− Évaluer la dose-réponse du guselkumab afin d’aider à sélectionner la dose d’utilisation pour la partie de phase 3 de ce protocole
− Évaluer l’efficacité du guselkumab sur l’amélioration des résultats vis-à-vis de l’examen endoscopique
− Évaluer la pharmacocinétique (PK), l’immunogénicité et la pharmacodynamique (PD) du traitement par guselkumab
Phase 3:
− Évaluer l’efficacité du guselkumab sur l’amélioration des résultats de l’examen endoscopique
− Évaluer l’impact du guselkumab sur la QdVLS
− Évaluer la PK, l’immunogénicité et la PD du traitement par 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 |
Phase 2 and Phase 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.
- Optional pharmacogenomic sub-study: 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. |
|
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 |
|
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 |
|
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) |
Phase 2: Variation du score de l' Indice d’activité de la maladie de Crohn (CDAI) par rapport au score de référence à la Semaine 12
Phase 3: rémission clinique à la Semaine 12 (définie comme un score 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) |
Phase 2:
− Rémission clinique à la Semaine 12 (définie comme un score CDAI < 150)
− Réponse clinique à la Semaine 12 (définie comme une réduction 100 points par rapport au score de référence CDAI ou un score CDAI < 150)
− Rémission des éléments PRO-2 à la Semaine 12 (définie comme un score quotidien moyen de fréquence des selles [FS] et un score quotidien moyen de douleur abdominale [DA])
− Réponse clinique des biomarqueurs à la Semaine 12 (réponse clinique basée sur le score CDAI et réduction 50 % par rapport à la référence du taux de CRP ou de calprotectine fécale)
− Réponse endoscopique à la Semaine 12 (mesurée par le score endoscopique simple pour la maladie de Crohn (SES-CD)). Le SES-CD est basé sur l'évaluation de 4 éléments endoscopiques à travers 5 segments ileocoloniques, avec un score total allant de 0 à 56)
Phase 3:
− Rémission clinique à la Semaine 48 (définie comme un score CDAI < 150)
− Rémission clinique durable à la Semaine 48 (définie comme un score CDAI < 150 pour toutes les visites entre la Semaine 12 et la Semaine 48)
− Rémission clinique sans corticoïdes à la Semaine 48 (définie comme un score CDAI < 150 à la semaine 48 et l’absence de prise de corticoïdes à la Semaine 48)
− Rémission des éléments PRO-2 aux Semaines 12 et 48 (basée sur un score quotidien moyen de fréquence des selles [FS] et un score quotidien moyen de douleur abdominale [DA])
− Réponse endoscopique à la Semaines 12 (mesurée par le score endoscopique simple pour la maladie de Crohn (SES-CD)).
− Réponse en termes de fatigue à la Semaine 12 (basée sur le formulaire PROMIS-Fatigue abrégé 7a) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 12 or 48 as listed above |
Semaine 12 ou 48 comme listés ci-dessus |
|
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 | 17 |
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 | No |
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 |
Austria |
Belarus |
Belgium |
Bosnia and Herzegovina |
Brazil |
Canada |
China |
Colombia |
Croatia |
Czech Republic |
France |
Georgia |
Germany |
Greece |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Latvia |
Lebanon |
Lithuania |
Macedonia, the former Yugoslav Republic of |
Netherlands |
New Zealand |
Poland |
Portugal |
Russian Federation |
Saudi Arabia |
Serbia |
Slovakia |
South Africa |
Spain |
Taiwan |
Tunisia |
Turkey |
Ukraine |
United Kingdom |
United States |
Jordan |
|
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
|
LVLS |
dernière visite du dernier patient |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 22 |
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 |