A Multicenter, Randomized, Double-Blind, Placebo Controlled Induction Study to Evaluate the Efficacy and Safety of Risankizumab in Participants With Moderately to Severely Active Ulcerative Colitis

Study Overview
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Brief Summary
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The objectives of Sub-Study 1 are to evaluate the efficacy, safety, and pharmacokinetics of risankizumab as induction treatment in subjects with moderately to severely active ulcerative colitis (UC), and to identify the appropriate induction dose of risankizumab for further evaluation in Sub-Study 2. The objective of Sub-Study 2 is to evaluate the efficacy and safety of risankizumab compared to placebo in inducing clinical remission in subjects with moderately to severely active UC.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo Controlled Induction Study to Evaluate the Efficacy and Safety of Risankizumab in Subjects With Moderately to Severely Active Ulcerative Colitis

Conditions
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Ulcerative Colitis (UC)

Intervention / Treatment
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* Drug: risankizumab IV
* Drug: placebo for risankizumab
* Drug: risankizumab SC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged >=18 to <= 80 years at the Baseline Visit. Where locally permissible, subjects 16 to < 18 years of age who meet the definition of Tanner stage 5 for development at the Baseline Visit. Confirmed diagnosis of ulcerative colitis (UC) for at least 3 months prior to Baseline. Active UC as assessed by Adapted Mayo Score and Endoscopic Subscore. Demonstrated intolerance or inadequate response to conventional therapy and tofacitinib (not a biologic) and one or more biologic therapies. Females must be postmenopausal for more than 1 year or surgically sterile or practicing specific forms of birth control. Exclusion Criteria: Participant with a current diagnosis of Crohn's disease (CD), inflammatory bowel disease-unclassified (IBD-U) or a history of radiation colitis or ischemic colitis. Participant receiving prohibited medications and treatment. Extent of inflammatory disease limited to the rectum as assessed by screening endoscopy. Participant with currently known complications of UC (e.g., megacolon). No known active Coronavirus Disease - 2019 (COVID-19) infection.

Ages Eligible for Study
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Minimum Age: 16 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Substudy 1, Induction 1: Double-blind Risankizumab Dose 1<br>Participants randomized to receive risankizumab dose 1 administered by intravenous (IV) infusion. | Drug: risankizumab IV<br>* risankizumab intravenous (IV) infusion<br>* Other names: BI 655066;|
| Experimental: Substudy 1, Induction 1: Double-blind Risankizumab Dose 2<br>Participants randomized to receive risankizumab dose 2 administered by intravenous (IV) infusion. | Drug: risankizumab IV<br>* risankizumab intravenous (IV) infusion<br>* Other names: BI 655066;|
| Experimental: Substudy 1, Induction 1: Double-blind Risankizumab Dose 3<br>Participants randomized to receive risankizumab dose 3 administered by intravenous (IV) infusion. | Drug: risankizumab IV<br>* risankizumab intravenous (IV) infusion<br>* Other names: BI 655066;|
| Placebo Comparator: Substudy 1, Induction 1: Double-blind Placebo<br>Participants randomized to receive placebo for risankizumab administered by intravenous (IV) infusion. | Drug: placebo for risankizumab<br>* placebo for risankizumab<br>|
| Experimental: Substudy 1, Induction 1: Open-label Risankizumab Dose 1<br>Participants receive risankizumab dose 1 administered by intravenous (IV) infusion. | Drug: risankizumab IV<br>* risankizumab intravenous (IV) infusion<br>* Other names: BI 655066;|
| Experimental: Substudy 1, Induction 2: Double-blind Risankizumab Dose 1(a)<br>Participants who received placebo with inadequate response in Induction 1 receive risankizumab dose 1 administered by intravenous (IV) infusion in Induction 2. | Drug: risankizumab IV<br>* risankizumab intravenous (IV) infusion<br>* Other names: BI 655066;|
| Experimental: Substudy 1, Induction 2: Double-blind Risankizumab Dose 1(b)<br>Participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab dose 1 administered by intravenous (IV) infusion in Induction 2. | Drug: risankizumab IV<br>* risankizumab intravenous (IV) infusion<br>* Other names: BI 655066;|
| Experimental: Substudy 1, Induction 2: Double-blind Risankizumab Dose 2<br>Participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab dose 2 administered by subcutaneous (SC) injection in Induction 2. | Drug: risankizumab SC<br>* risankizumab subcutaneous (SC) injection<br>* Other names: BI 655066;|
| Experimental: Substudy 1, Induction 2: Double-blind Risankizumab Dose 3<br>Participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab dose 3 administered by subcutaneous (SC) injection in Induction 2. | Drug: risankizumab SC<br>* risankizumab subcutaneous (SC) injection<br>* Other names: BI 655066;|
| Experimental: Substudy 2, Induction 1: Double-blind Risankizumab Dose 1<br>Participants randomized to receive risankizumab dose 1 administered by intravenous (IV) infusion. | Drug: risankizumab IV<br>* risankizumab intravenous (IV) infusion<br>* Other names: BI 655066;|
| Placebo Comparator: Substudy 2, Induction 1: Double-blind Placebo<br>Participants randomized to receive placebo for risankizumab administered by intravenous (IV) infusion. | Drug: risankizumab IV<br>* risankizumab intravenous (IV) infusion<br>* Other names: BI 655066;Drug: placebo for risankizumab<br>* placebo for risankizumab<br>|
| Experimental: Substudy 2, Induction 2: Double-blind Risankizumab Dose 1(a)<br>Participants who received placebo with inadequate response in Induction 1 randomized to receive risankizumab dose 1 administered by intravenous (IV) infusion in Induction 2. | Drug: risankizumab IV<br>* risankizumab intravenous (IV) infusion<br>* Other names: BI 655066;|
| Experimental: Substudy 2, Induction 2: Double-blind Risankizumab Dose 1(b)<br>Participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab dose 1 administered by intravenous (IV) infusion in Induction 2. | Drug: risankizumab IV<br>* risankizumab intravenous (IV) infusion<br>* Other names: BI 655066;|
| Experimental: Substudy 2, Induction 2: Double-blind Risankizumab Dose 2<br>Participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab dose 2 administered by subcutaneous (SC) injection in Induction 2. | Drug: risankizumab SC<br>* risankizumab subcutaneous (SC) injection<br>* Other names: BI 655066;|
| Experimental: Substudy 2, Induction 2: Double-blind Risankizumab Dose 3<br>Participants who received risankizumab with inadequate response in Induction 1 randomized to receive risankizumab dose 3 administered by subcutaneous (SC) injection in Induction 2. | Drug: risankizumab SC<br>* risankizumab subcutaneous (SC) injection<br>* Other names: BI 655066;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sub-Study 1 and Sub-Study 2: Percentage of Participants Achieving Clinical Remission per Adapted Mayo Score | Clinical remission per adapted Mayo Score. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sub-Study 1: Percentage of Participants Achieving Endoscopic Improvement | Endoscopic improvement per endoscopy subscore. | Week 12 | 
| Sub-Study 1: Percentage of Participants Achieving Clinical Remission per Full Mayo Score in Participants with a Full Mayo Score of 6 to 12 at Baseline | Clinical remission per Full Mayo Score. | Week 12 | 
| Sub-Study 1: Percentage of Participants Achieving Clinical Response per Adapted Mayo Score | Clinical response per adapted Mayo Score. | Week 12 | 
| Sub-Study 1: Percentage of Participants Achieving Clinical Response per Partial Adapted Mayo Score | Clinical response per Partial Adapted Mayo Score (without endoscopy). | Week 4 | 
| Sub-Study 1: Percentage of Participants Achieving Endoscopic Remission | Endoscopic remission per endoscopy subscore. | Week 12 | 
| Sub-Study 1: Percentage of Participants with Hospitalization | Participants with an event that results in admission to the hospital. | Through Week 12 | 
| Sub-Study 1: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR) | Mucosal healing defined as endoscopic and histologic remission. | Week 12 | 
| Sub-Study 1: Change in Ulcerative Colitis Symptom Questionnaire (UC-SQ) | The US-SQ is a patient questionnaire to assess severity of Crohn's symptoms. | Baseline Through Week 12 | 
| Sub-Study 1: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) | The IBDQ is used to assess the quality of life of patients with inflammatory bowel disease. | Baseline Through Week 12 | 
| Sub-Study 1: Change in Short Form-36 (SF-36) | The SF-36 is an indicator of overall health status. | Baseline Through Week 12 | 
| Sub-Study 1: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) | The FACIT-Fatigue is a validated tool that measures an individual's level of fatigue during their usual daily activities over the past week. | Baseline Through Week 12 | 
| Sub-Study 1: Percentage of Participants Undergoing Ulcerative Colitis (UC)-related Surgeries | Participants who underwent surgery related to UC. | Through Week 12 | 
| Sub-Study 2: Percentage of Participants Achieving Clinical Response per Adapted Mayo Score | Clinical response per adapted Mayo Score. | Week 12 | 
| Sub-Study 2: Percentage of Participants Achieving Endoscopic Improvement | Endoscopic improvement per endoscopy subscore. | Week 12 | 
| Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Improvement (HEMI) | Endoscopic subscore of 0 or 1 without evidence of friability and Geboes score ≤ 3.1) at Week 12 | Week 12 | 
| Sub-Study 2: Percentage of Participants Achieving Endoscopic Remission | Endoscopic remission per endoscopy subscore. | Week 12 | 
| Sub-Study 2: Percentage of Participants Achieving Clinical Response per Partial Adapted Mayo Score at Week 4 | Clinical response per Partial Adapted Mayo Score (without endoscopy). | Week 4 | 
| Sub-Study 2: Percentage of Participants Achieving No Bowel Urgency | Percentage of participants who reported no bowel urgency. | Week 12 | 
| Sub-Study 2: Percentage of Participants Achieving No Abdominal Pain | Percentage of participants who reported no abdominal pain. | Week 12 | 
| Sub-Study 2: Percentage of Participants Achieving Histologic Endoscopic Mucosal Remission (HEMR): Endoscopy Subscore of 0 and Geboes Score < 2.0) at Week 12 | Mucosal healing defined as endoscopic and histologic remission. | Week 12 | 
| Sub-Study 2: Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) | The FACIT-Fatigue is a validated tool that measures an individual's level of fatigue during their usual daily activities over the past week. | Baseline to Week 12 | 
| Sub-Study 2: Change in Inflammatory Bowel Disease Questionnaire (IBDQ) total score | The IBDQ is used to assess the quality of life of patients with inflammatory bowel disease. | Baseline to Week 12 | 
| Sub-Study 2: Occurrence of UC-related Hospitalizations | Participants with an UC-related event that results in admission to the hospital. | Baseline Through Week 12 | 
| Sub-Study 2: Percentage of Participants Achieving No Nocturnal Bowel Movements | Percentage of participants who reported no nocturnal bowel movements. | Week 12 | 
| Sub-Study 2: Percentage of Participants Achieving No Tenesmus | Percentage of participants who reported no tenesmus. | Week 12 | 
| Sub-Study 2: Change in Number of Fecal Incontinence Episodes per Week | Change in number of fecal incontinence episodes per week. | Baseline to Week 12 | 
| Sub-Study 2: Change in Number of Days per Week with Sleep Interrupted due to UC Symptoms | Change in number of days per week with sleep interrupted due to UC symptoms. | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABBV-066, BI 655066