A Study of the Efficacy and Safety of Risankizumab in Participants With Crohn's Disease

Study Overview
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Brief Summary
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The study consists of 4 sub-studies, as follows: Sub-study 1 (Randomized, double-blind, placebo controlled study) to evaluate the efficacy and safety of risankizumab versus placebo as maintenance therapy in participants with moderately to severely active Crohn's disease (CD) who responded to intravenous risankizumab induction treatment in Study M16-006 or Study M15-991; Sub-study 2 (Randomized, exploratory maintenance study) to evaluate the efficacy and safety of two different dosing regimens for risankizumab as maintenance therapy in participants who responded to induction treatment in Study M16-006 or Study M15-991; Sub-study 3 (Open-label, long-term extension study) to evaluate long-term safety of risankizumab in participants who completed Sub-study 1, Sub-study 2, another AbbVie risankizumab Crohn's disease study, or participants who responded to induction treatment in Study M16-006 or Study M15-991 with no final endoscopy due to the Covid-19 pandemic. Additional objectives are to further investigate long-term efficacy and tolerability of risankizumab; Sub-study 4 (Open-label On Body Injector (OBI) administration and long-term extension study) to evaluate patient-reported outcomes, efficacy, safety, tolerability, and pharmacokinetics of risankizumab administered via OBI in participants who are receiving maintenance treatment with risankizumab. OL CTE to ensure uninterrupted care in accordance with local regulations until risankizumab is commercially available for participants who completed Sub-study 3, Sub-study 4.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo Controlled 52-Week Maintenance and an Open-Label Extension Study of the Efficacy and Safety of Risankizumab in Subjects With Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Placebo for Risankizumab SC
* Drug: Risankizumab IV
* Drug: Placebo for Risankizumab IV
* Drug: Risankizumab SC
* Drug: Risankizumab On-Body Injector (OBI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who have entered and completed Study M16-006 or Study M15-991 or other AbbVie risankizumab Crohn's disease study. Participants have completed the study M16-006 or M15-991 and have achieved clinical response. Sub-Study 4: Participants receiving maintenance treatment in Sub-study 3 and willing to comply with the requirements of Sub-study 4, including self-administration of sub-cutaneous injections using the on-body injector (OBI). Participant has received at least 16 weeks of stable dosing with risankizumab in Sub-study 3 (i.e., no rescue within 16 weeks and participant has surpassed the 72-week mark). Exclusion Criteria: Participants should not be enrolled in Study M16-000 with high grade colonic dysplasia or colon cancer identified during Study M15-991, Study M16-006 or another AbbVie risankizumab Crohn's disease study if the final endoscopy was performed prior to enter Study M16-000 OR is considered by the Investigator, for any reason, to be an unsuitable candidate for the study. Participant who has a known hypersensitivity to risankizumab or the excipients of any of the study drugs or the ingredients of Chinese hamster ovary (CHO), OR had an adverse event (AE) during Studies M16-006, M15-991 or another AbbVie risankizumab Crohn's disease study that in the Investigator's judgment makes the participant unsuitable for this study. Participant is not in compliance with prior and concomitant medication requirements throughout Studies M16-006, M15-991 or another AbbVie risankizumab Crohn's disease study. Confirmed positive urine pregnancy test at the Final Visit of Study M16-006, Study M15-991 or another AbbVie risankizumab Crohn's disease study. Have a known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly. Any active or chronic recurring infections based on the Investigator's assessment makes the participant an unsuitable candidate for the study.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Double-blind Placebo for Risankizumab (Sub-Study 1)<br>Participants randomized to receive double-blind placebo for risankizumab for 52 weeks. | Drug: Placebo for Risankizumab SC<br>* Placebo for Risankizumab SC Subcutaneous (SC) Injection<br>|
| Experimental: Double-blind Risankizumab Dose 1 (Sub-Study 1)<br>Participants randomized to receive double-blind risankizumab dose 1 for 52 weeks. | Drug: Risankizumab SC<br>* Risankizumab SC Subcutaneous (SC) injection<br>* Other names: SKYRIZI;|
| Experimental: Double-blind Risankizumab Dose 2 (Sub-Study 1)<br>Participants randomized to receive double-blind risankizumab dose 2 for 52 weeks. | Drug: Risankizumab SC<br>* Risankizumab SC Subcutaneous (SC) injection<br>* Other names: SKYRIZI;|
| Experimental: Maintenance Risankizumab Dose 1 (Sub-Study 2)<br>Participants will receive double-blind subcutaneous (SC)risankizumab dose 1 and intravenous placebo at Week 0 followed by open-label SC risankizumab dose 1 from Week 8 through Week 52. | Drug: Placebo for Risankizumab IV<br>* Placebo for Risankizumab IV Intravenous (IV) infusion<br>Drug: Risankizumab SC<br>* Risankizumab SC Subcutaneous (SC) injection<br>* Other names: SKYRIZI;|
| Experimental: Maintenance Risankizumab Dose 2 (Sub-Study 2)<br>Participants will receive double-blind subcutaneous placebo and intravenous risankizumab dose 3 at Week 0 followed by open-label SC risankizumab dose 1 from Week 8 through Week 52. | Drug: Placebo for Risankizumab SC<br>* Placebo for Risankizumab SC Subcutaneous (SC) Injection<br>Drug: Risankizumab IV<br>* Risankizumab IV Intravenous (IV) infusion<br>* Other names: SKYRIZI;Drug: Risankizumab SC<br>* Risankizumab SC Subcutaneous (SC) injection<br>* Other names: SKYRIZI;|
| Experimental: Open-label Risankizumab (Sub-Study 3)<br>Participants who completed Sub-study 1 or Sub-study 2 or other AbbVie risankizumab Crohn's disease study or M16-006 or M15-991 without endoscopy will receive open-label risankizumab dose 1 or dose 2 depending on their preceding study beginning at Week 56. | Drug: Risankizumab SC<br>* Risankizumab SC Subcutaneous (SC) injection<br>* Other names: SKYRIZI;|
| Experimental: Risankizumab On-Body Injector and Open Label (Sub-Study 4)<br>Participants in Sub-study 3 who meet eligible criteria for Sub-study 4 will receive risankizumab dose 1 or dose 2 via on-body injectors on Weeks 0,8 and 16. Beginning Week 24, participants will receive risankizumab dose 1 or dose 2 via pre-filled syringes Q8W. | Drug: Risankizumab SC<br>* Risankizumab SC Subcutaneous (SC) injection<br>* Other names: SKYRIZI;Drug: Risankizumab On-Body Injector (OBI)<br>* Subcutaneous (SC) injection; on-body injector (OBI)<br>* Other names: SKYRIZI;|
| Experimental: CTE: Open Label Continuous Treatment Extension<br>Participants who tolerate and derive benefit from receiving risankizumab and complete Sub-study 3 or Sub-study 4 will receive risankizumab dose 1 or dose 2 Q8W. | Drug: Risankizumab SC<br>* Risankizumab SC Subcutaneous (SC) injection<br>* Other names: SKYRIZI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sub-Study 1: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission | The CDAI is used to evaluate disease activity in patients with Crohn's disease. The CDAI clinical remission is defined as a CDAI score of < 150. | Week 52 | 
| Sub-Study 1: Percentage of Participants With Endoscopic Response | Endoscopic response defined as decrease from Baseline of the induction study in Simple Endoscopic Score for Crohn's Disease (SES-CD). | Week 52 | 
| Sub-Study 3: Number of Participants With Adverse Events | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. 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 subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent AEs are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section. | Up to Week 220 | 
| Sub-Study 4: Percentage of Participants With an Observer Rating of Successful Participant Self Administration | Participant who successfully completed the sequence of critical steps in the instructions for use (IFU) without errors to administer study drug via the OBI at Week 0 and 16. | Up to Week 16 | 
| Sub-Study 4: Percentage of Participants who had no Potential Hazards | Measured by an observer on the possible use-related hazards checklist for self-administration with OBI at Week 0 and Week 16. | Up to Week 16 | 
| Sub-Study 4: Percentage of Participants Rating of Acceptability Using Self-Injection Assessment Questionnaire (SIAQ) at Weeks 0, 8, 16 | SIAQ evaluations consist of the PRE module, which is self-completed immediately before the first OBI self-injection at baseline, and the POST module, which is self-completed 20 to 40 min following injections at Weeks 0, 8, 16. These modules are completed by participants while alone in a quiet environment. Participants rate each item of the SIAQ. The ratings are later transformed to scores ranging from 0 (worst experience) to 10 (best experience). The domain score is the mean of the item scores included in the domain. Domain scores are calculated only if at least half of the domain items are completed. Item and domain scores from the PRE module are compared with the corresponding item and domain scores from the POST modules. | Up to Week 16 | 
| Sub-Study 4: Percentage of Participants in CDAI Clinical Remission at Week 0, 16 | Clinical remission per average daily stool frequency (SF) and average daily abdominal pain (AP) score. | Up to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sub-Study 1: Percentage of Participants With Clinical Remission | Clinical remission per average daily stool frequency (SF) and average daily AP score. | Week 52 | 
| Sub-Study 1: Percentage of Participants With CDAI Clinical Remission Among Participants With CDAI Clinical Remission in Week 0 | The CDAI is used to evaluate disease activity in patients with Crohn's disease | Week 52 | 
| Sub-Study 1: Percentage of Participants With Ulcer-Free Endoscopy | Endoscopic healing was assessed using SES-CD. | Week 52 | 
| Sub-Study 1: Percentage of Participants With Endoscopic Remission | Endoscopic Remission is defined as SES-CD <= 4 and at least a 2 point reduction versus baseline and no subscore greater than 1 in any individual variable, as scored by a central reviewer | Week 52 | 
| Sub-Study 1: Change From Baseline of Induction 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. | Week 52 | 
| Sub-Study 1: Percentage of Participants Who Discontinued Corticosteroid Use for 90 Days and Achieved Clinical Remission in Participants Taking Steroids at Baseline | Participants who discontinued corticosteroid use and achieved clinical remission per average daily SF and average daily AP score. | Week 52 | 
| Sub-Study 1: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response | The CDAI is used to evaluate disease activity in patients with Crohn's disease. | Week 52 | 
| Sub-Study 1: Percentage of Participants With Stool Frequency (SF) Remission | SF Remission is defined by an average daily SF <= 2.8 and not worse than baseline. | Week 52 | 
| Sub-Study 1: Percentage of Participants With Abdominal Pain (AP) Remission | AP Remission is defined by an average daily AP <= 1 and not worse than baseline. | Week 52 | 
| Sub-Study 1: Percentage of Participants With CDAI Clinical Remission and Endoscopic Response | The CDAI is used to evaluate disease activity in patients with Crohn's disease. The CDAI clinical remission is defined as a CDAI score of < 150. Endoscopic response defined as decrease from baseline of > 50% of the induction study in Simple Endoscopic Score for Crohn's Disease (SES-CD). | Week 52 | 
| Sub-Study 1: Percentage of Participants With Deep Remission | Deep remission defined as participants with both clinical remission (per average daily SF and average daily AP score) and endoscopic remission (assessed using SES-CD). | Week 52 | 
| Sub-Study 1: Percentage of Participants With Exposure Adjusted Occurrence of CD-related Hospitalizations From Week 0 Through Week 52 | Participants with an event that results in admission to the hospital. | Up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Risankizumab, ABBV-066, BI 655066, SKYRIZI, Crohn's Disease (CD)