Study Comparing Intravenous (IV)/Subcutaneous (SC) Risankizumab to IV/SC Ustekinumab to Assess Change in Crohn's Disease Activity Index (CDAI) in Adult Participants With Moderate to Severe Crohn's Disease (CD)

Study Overview
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Brief Summary
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Crohn's disease (CD) is a long-lasting condition causing inflammation that can affect any part of the gut. This study will evaluate how well risankizumab works compared to ustekinumab. This study will assess change in Crohn's Disease Activity Index (CDAI). Risankizumab is an investigational drug being developed for the treatment of Crohn's Disease (CD). Ustekinumab is an approved drug for the treatment of moderate and severe CD. Participants are randomly assigned to one of the three treatment groups. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to ustekinumab. Around 508 adult participants with moderate to severe CD will be enrolled in approximately 307 sites worldwide. In Part 1, participants assigned to risankizumab will receive intravenous (IV) doses of risankizumab at Week 0, 4,8 and subcutaneous (SC) doses every 8 weeks thereafter through Week 48. Participants assigned to ustekinumab will receive intravenous (IV) dose of ustekinumab at Week 0 and subcutaneous (SC) doses every 8 weeks thereafter through Week 48. In Part 2, participants who received risankizumab in Part 1 and completed the Week 48 visit will continue to receive SC risankizumab for up to an additional 220 weeks. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Official Title
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A Phase 3, Multicenter, Randomized, Efficacy Assessor-Blinded Study of Risankizumab Compared to Ustekinumab for the Treatment of Adult Subjects With Moderate to Severe Crohn's Disease Who Have Failed Anti-TNF Therapy

Conditions
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Crohn's Disease (CD)

Intervention / Treatment
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* Drug: Risankizumab
* Drug: Risankizumab
* Drug: Ustekinumab
* Drug: Ustekinumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of Crohn's disease (CD) for at least 3 months prior to Baseline. Crohn's disease activity index (CDAI) score 220 - 450 at Baseline. Confirmed diagnosis of moderate to severe Crohn's Disease as assessed by stool frequency (SF), abdominal pain (AP) score, and Simple Endoscopic score for CD (SES-CD). Demonstrated intolerance or inadequate response to one or more anti-tumor necrosis factor (TNF) therapies. Exclusion Criteria: Current diagnosis of ulcerative colitis or indeterminate colitis. Receipt of CD approved biologic agents prior to Baseline (as detailed in protocol), or any investigational biologic or other agent or procedure prior to Baseline (as detailed in protocol). Prior exposure to p19 and/or p40 inhibitors (e.g., risankizumab and ustekinumab). Currently know complications of CD (strictures, short bowel, etc).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Risankizumab Dose A Followed by Dose B<br>Participants will receive intravenous risankizumab dose A at Week 0, 4 ,8 followed by subcutaneous (SC) risankizumab dose B every 8 weeks through Week 48. Participants who complete the Week 48 visit will continue SC risankizumab for up to an additional 220 weeks. | Drug: Risankizumab<br>* Intravenous (IV) Infusion<br>* Other names: SKYRIZI;Drug: Risankizumab<br>* Subcutaneous (SC) Injection<br>* Other names: SKYRIZI;|
| Active Comparator: Ustekinumab<br>Participants will receive weight-based intravenous ustekinumab at Week 0 followed by subcutaneous ustekinumab every 8 weeks through Week 48. | Drug: Ustekinumab<br>* Intravenous (IV) infusion<br>Drug: Ustekinumab<br>* Subcutaneous (SC) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Clinical Remission at Week 24 | Clinical remission is defined as Crohn's disease activity index (CDAI)<150. | Week 24 | 
| Percentage of Participants Achieving Endoscopic Remission | Endoscopic remission is defined as Simple Endoscopic Score for Crohn's Disease (SES-CD) <= 4 and at least a 2-point reduction versus Baseline and no sub score greater than 1 in any individual variable, as scored by a central reviewer. | Week 48 | 
| Number of Participants Reporting Adverse Events | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug. | Up to 220 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Clinical Remission at Week 48 | Clinical remission is defined as Crohn's disease activity index (CDAI)<150. | Week 48 | 
| Percentage of Participants Achieving Endoscopic Response at Week 48 | Endoscopic response is defined as decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) > 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline). | Week 48 | 
| Percentage of Participants Achieving Endoscopic Response at Week 24 | Endoscopic response is defined as decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) > 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline). | Week 24 | 
| Percentage of Participants Achieving Steroid-Free Endoscopic Remission | Steroid-free endoscopic remission is defined as participants with endoscopic remission and not receiving steroids at Week 48. | Week 48 | 
| Percentage of Participants Achieving Steroid-Free Clinical Remission | Steroid-free clinical remission is defined as participants with clinical remission and not receiving steroids at Week 48. | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease (CD), Risankizumab, Ustekinumab, SKYRIZI