A Study of the Efficacy and Safety of Guselkumab in Participants With Moderately to Severely Active Crohn's Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the clinical efficacy (GALAXI 1), clinical and endoscopic efficacy (GALAXI 2 and GALAXI 3) and safety of guselkumab in participants with Crohn's disease.

Detailed Description
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This program consists of 3 separate studies: a 48-week Phase 2 dose-ranging study (GALAXI 1) and two 48-week Phase 3 confirmatory studies (GALAXI 2 and GALAXI 3). In Phase 2, safety and efficacy of guselkumab dose regimens will be evaluated to support the selection of induction and maintenance dose regimens for confirmatory evaluation in Phase 3. Participants who complete the 48-week Phase 2 or Phase 3 studies may be eligible to enter the long term extension (LTE). Throughout the 3 studies, efficacy, pharmacokinetic, biomarkers, and safety will be assessed.

Official Title
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A Phase 2/3, Randomized, Double-blind, Placebo- and Active-controlled, Parallel-group, Multicenter Protocol to Evaluate the Efficacy and Safety of Guselkumab in Participants With Moderately to Severely Active Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Guselkumab Dose 1
* Drug: Guselkumab Dose 2
* Drug: Guselkumab Dose 3
* Drug: Guselkumab Dose 4
* Drug: Guselkumab Dose 5
* Drug: Guselkumab
* Drug: Ustekinumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 2 (GALAXI 1): Group 1 (Guselkumab)<br>Participants will receive guselkumab (Dose 1) by intravenous (IV) infusion, followed by guselkumab (Dose 2) by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the Long-Term Extension (LTE) phase and continue to receive guselkumab. | Drug: Guselkumab Dose 1<br>* Guselkumab will be administered by IV infusion.<br>Drug: Guselkumab Dose 2<br>* Guselkumab will be administered by SC injection.<br>|
| Experimental: Phase 2 (GALAXI 1): Group 2 (Guselkumab)<br>Participants will receive guselkumab (Dose 3) by intravenous (IV) infusion, followed by guselkumab (Dose 2) by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the LTE phase and continue to receive guselkumab. | Drug: Guselkumab Dose 2<br>* Guselkumab will be administered by SC injection.<br>Drug: Guselkumab Dose 3<br>* Guselkumab will be administered by IV infusion.<br>|
| Experimental: Phase 2 (GALAXI 1): Group 3 (Guselkumab)<br>Participants will receive guselkumab (Dose 4) by intravenous (IV) infusion, followed by guselkumab (Dose 5) by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the LTE phase and continue to receive guselkumab. | Drug: Guselkumab Dose 4<br>* Guselkumab will be administered by IV infusion.<br>Drug: Guselkumab Dose 5<br>* Guselkumab will be by SC injection.<br>|
| Active Comparator: Phase 2 (GALAXI 1): Group 4 (Ustekinumab)<br>Participants will receive ustekinumab by intravenous (IV) infusion, followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue ustekinumab may enter the LTE and continue to receive ustekinumab. | Drug: Ustekinumab<br>* Ustekinumab will be administered by IV infusion and SC injection.<br>|
| Experimental: Phase 2 (GALAXI 1): Group 5 (Placebo/Ustekinumab)<br>Participants will receive placebo administered by intravenous (IV) infusion. At Week 12, non-responders will receive active treatment (Ustekinumab) administered by intravenous (IV) infusion followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue placebo/ustekinumab may enter the LTE and continue to receive placebo/ustekinumab. | Drug: Ustekinumab<br>* Ustekinumab will be administered by IV infusion and SC injection.<br>Drug: Placebo<br>* Placebo will be administered as IV infusion.<br>|
| Experimental: Phase 3 (GALAXI 2 and 3): Group 1 and Group 2 (Guselkumab)<br>Participants will receive guselkumab by intravenous (IV) infusion, followed by guselkumab by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the LTE phase and continue to receive guselkumab. | Drug: Guselkumab<br>* Guselkumab will be administered by IV infusion and SC injection.<br>|
| Active Comparator: Phase 3 (GALAXI 2 and 3): Group 3 (Ustekinumab)<br>Participants will receive ustekinumab by intravenous (IV) infusion, followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue ustekinumab may enter the LTE phase and continue to receive ustekinumab. | Drug: Ustekinumab<br>* Ustekinumab will be administered by IV infusion and SC injection.<br>|
| Experimental: Phase 3 (GALAXI 2 and 3): Group 4 (Placebo/Ustekinumab)<br>Participants will receive placebo administered by intravenous (IV) infusion. At Week 12, non-responders will receive active treatment (ustekinumab) administered by intravenous (IV) infusion followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue placebo/ustekinumab may enter the LTE and continue to receive placebo/ustekinumab. | Drug: Ustekinumab<br>* Ustekinumab will be administered by IV infusion and SC injection.<br>Drug: Placebo<br>* Placebo will be administered as IV infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2: Change from Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 12 | The CDAI score will be assessed by collecting information on 8 different Crohn's disease-related variables, with scores ranging from 0 to approximately 600. A decrease over time indicates improvement in disease activity. | Baseline and Week 12 | 
| Phase 3: Clinical Response at Week 12 and Clinical Remission at Week 48 | Clinical response and clinical remission based on CDAI score. | Baseline to Week 48 | 
| Phase 3: Clinical Response at Week 12 and Endoscopic Response at Week 48 | Clinical response based on CDAI score and endoscopic response based on Simple Endoscopic Score for Crohn's Disease (SES-CD). | Baseline to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2: Clinical Remission at Week 12 | Clinical remission is defined as CDAI score <150. | Week 12 | 
| Phase 2: Clinical Response at Week 12 | Clinical response is defined as >= 100-point reduction from baseline in CDAI score or CDAI score <150. | Week 12 | 
| Phase 2 and Phase 3: Patient-Reported Outcome (PRO)-2 Remission at Week 12 | PRO-2 remission is defined based on average daily stool frequency (SF), average daily abdominal pain (AP) score and no worsening of AP or SF from baseline. | Week 12 | 
| Phase 2: Clinical-Biomarker Response at Week 12 | Clinical-biomarker response is defined using clinical response based on the CDAI score and reduction from baseline in C-reactive protein (CRP) or fecal calprotectin. | Week 12 | 
| Phase 2: Endoscopic Response at Week 12 | Endoscopic Response is measured by the 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. | Week 12 | 
| Phase 3: Clinical Response at Week 4 | Clinical response based on CDAI score. | Week 4 | 
| Phase 3: Clinical Remission at Week 12 | Clinical remission based on CDAI score. | Week 12 | 
| Phase 3: Endoscopic Response at Week 12 | Endoscopic response based on SES-CD score. | Week 12 | 
| Phase 3: Fatigue Response at Week 12 | Fatigue response will be based on the Patient-Reported Outcomes Measurement Information System (PROMIS). | Week 12 | 
| Phase 3: Clinical Remission at Week 12 and Endoscopic Response at Week 12 | Clinical remission based on CDAI score and endoscopic response based on SES-CD score. | Week 12 | 
| Phase 3: Endoscopic Remission at Week 12 | Endoscopic remission based on SES-CD score. | Week 12 | 
| Phase 3: Clinical Response at Week 12 and Corticosteroid-Free Clinical Remission at Week 48 | Clinical response based on CDAI score; corticosteroid-free clinical remission based on CDAI score and corticosteroid concomitant medications. | Baseline to Week 48 | 
| Phase 3:Clinical Response at Week 12 and Endoscopic Remission at Week 48 | Clinical response based on CDAI and endoscopic remission based on SES-CD. | Baseline to Week 48 | 
| Phase 3: Clinical Remission at Week 48 | Clinical remission based on CDAI score. | Week 48 | 
| Phase 3: Endoscopic Response at Week 48 | Endoscopic response based on SES-CD. | Week 48 | 
| Phase 3: Clinical Remission at Week 48 and Endoscopic Response at Week 48 | Clinical remission based on CDAI score and endoscopic response based on SES-CD score. | Week 48 | 
| Phase 3: Endoscopic Remission at Week 48 | Endoscopic remission based on SES-CD score. | Week 48 | 
| Phase 3: Deep Remission at Week 48 | Deep remission is defined as clinical remission and endoscopic remission. | Week 48 |