E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderately to Severely Active Crohn's Disease |
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E.1.1.1 | Medical condition in easily understood language |
Inflammatory bowel disease (IBD) |
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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 |
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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 |
Phase 2: - To evaluate the clinical efficacy of guselkumab in participants with Crohn’s disease - To evaluate the safety of guselkumab
Phase 3: - To evaluate the clinical and endoscopic efficacy of guselkumab in participants with Crohn’s disease - To evaluate the safety of guselkumab |
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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 impact of guselkumab on HRQOL - To evaluate the PK, immunogenicity, and PD of guselkumab therapy |
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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 |
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.
Phase 2 (GALAXI 1) LTE study: - Real-life patient-handling sub-study: open-label substudy, whose purpose is to assess the ability of participants or their caregivers to perform guselkumab administration with either the 2.0 mL PFS-U or 2.0 mL PFS-Y in the standard of care setting (eg, at home or in the clinic), and to assess the reliability of each drug-device. When the Phase 2 study is unblinded, only those participants who are still in the Phase 2 LTE on the appropriate guselkumab dose will participate in this substudy.
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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 |
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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 - Any medical contraindications preventing study participation |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase 2: Change from baseline in the CDAI score at Week 12
Phase 3: Global co-primary endpoints: - clinical response at Week 12 and clinical remission at Week 48 - clinical response at Week 12 and endoscopic response at Week 48
Regional co-primary endpoints: - clinical remission at Week 12 - endoscopic response at Week 12
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Global: Week 12 and Week 48 Regional: Week 12
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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: Global Major Secondary Endpoints: Short-term efficacy, guselkumab versus placebo - Clinical response at Week 4 - Clinical remission at Week 12 - Endoscopic response at Week 12 - Fatigue response at Week 12 - Clinical remission at Week 12 and endoscopic response at Week 12 - Endoscopic remission (Global definition) at Week 12
Long-term, guselkumab versus placebo: - Clinical response at Week 12 and corticosteroid-free clinical remission at Week 48 - Clinical response at Week 12 and endoscopic remission (Global definition) at Week 48
Long-term, guselkumab versus ustekinumab: - Clinical remission at Week 48 - Endoscopic response at Week 48 - Clinical remission at Week 48 and endoscopic response at Week 48 - Endoscopic remission (Global definition) at Week 48 - Deep remission (Global definition) at Week 48
Regional Major Secondary Endpoints: Short-term efficacy, guselkumab versus placebo: - PRO-2 remission at Week 12 - Fatigue response at Week 12 - Endoscopic remission (Regional definition) at Week 12
Long-term, guselkumab versus placebo: - Corticosteroid-free clinical remission at Week 48 - Endoscopic response at Week 48
Long-term, guselkumab versus ustekinumab: - Endoscopic remission (Regional definition) at Week 48 - Clinical remission at Week 48 - Endoscopic response at Week 48 - Durable clinical remission at Week 48 - PRO-2 remission at Week 48 - Clinical remission at Week 48 and endoscopic response at Week 48 - Corticosteroid-free remission at Week 48
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 4, 12 or 48 as listed above |
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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 | 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 | 12 |
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 |
Brazil |
Canada |
China |
Colombia |
India |
Israel |
Japan |
Jordan |
Korea, Republic of |
Lebanon |
New Zealand |
Saudi Arabia |
South Africa |
Taiwan |
Tunisia |
United States |
Belarus |
Bosnia and Herzegovina |
Georgia |
North Macedonia |
Russian Federation |
Turkey |
Ukraine |
Serbia |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
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 |