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

The primary objective of this Phase 3, multicenter, randomized, efficacy assessor-blinded study is to compare the **efficacy** and safety of **risankizumab** versus **ustekinumab** over 48 weeks for the treatment of adult subjects with moderate to severe **Crohn's Disease** who have failed anti-TNF therapy. This comparison is clinically relevant as it aims to identify a more effective treatment option for patients who have not responded to existing therapies, potentially improving disease management and patient outcomes.

The study also aims to evaluate the long-term safety of risankizumab up to 220 weeks in subjects who received risankizumab during the initial phase and have completed the Week 48 visit. Additionally, the Continuous Treatment Extension (CTE) seeks to provide continuous treatment with risankizumab for Part 2 completers, ensuring uninterrupted care until the treatment is commercially available or accessible locally. The CTE also aims to continue the investigation and evaluation of long-term safety data for risankizumab.

The clinical trial involves a total of **274 participants** diagnosed with **Crohn's Disease**, specifically targeting adults aged between 18 and 80 years. The study population includes both male and female subjects who have a confirmed diagnosis of moderate to severe Crohn's Disease for at least three months prior to the baseline visit. Participants were selected based on their demonstrated intolerance or inadequate response to one or more anti-TNF therapies. The trial includes individuals with a Crohn's Disease Activity Index (CDAI) score ranging from 220 to 450 at baseline, assessed by stool frequency, abdominal pain score, and Simple Endoscopic Score for Crohn's Disease (SES-CD). The study population is characterized by a diverse age range and includes a vulnerable population, ensuring a comprehensive evaluation of the treatment's efficacy and safety. Relevant lifestyle considerations such as diet, physical activity, or habits are not specified in the provided data. Key inclusion criteria include adherence to contraception recommendations for female participants.

The clinical trial is a **randomized**, efficacy assessor-blinded study designed to evaluate the efficacy and safety of **risankizumab** compared to **ustekinumab** in adult subjects with moderate to severe **Crohn's Disease** who have failed anti-TNF therapy. The trial is structured in two parts, with Part 1 focusing on a 48-week comparison of the two treatments, and Part 2 extending to evaluate the long-term safety of risankizumab up to 220 weeks. The trial also includes a Continuous Treatment Extension (CTE) to ensure uninterrupted care for participants who complete Part 2, until the treatment becomes commercially available or participants can transition to a Continued Treatment for Trial Participants (CTTP) Open Label Extension (OLE) study.

The trial is expected to last until October 31, 2027, with recruitment having started on October 31, 2020. Participants will be involved in the study for a maximum of 220 weeks, depending on their progression through the trial phases. The study includes several key visits: an inclusion (screening) visit to confirm eligibility, regular follow-up visits to monitor treatment efficacy and safety, and an end-of-study visit to conclude participation. The primary endpoints include achieving clinical remission at Week 24 and endoscopic remission at Week 48, while secondary endpoints focus on the superiority of risankizumab over ustekinumab in achieving various remission and response criteria at specified time points.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The trial's design ensures that all participants receive either risankizumab or ustekinumab, with the former being administered as a **solution for infusion** or **injection in pre-filled syringe**, and the latter as a **solution for injection in pre-filled syringe** or **concentrate for solution for infusion**. The study aims to provide comprehensive data on the comparative efficacy and long-term safety of these treatments in managing Crohn's Disease.

The clinical trial involves the administration of **Risankizumab**, a biologic agent of protein origin, in two pharmaceutical forms. The first form is a **solution for infusion**, administered intravenously. The maximum daily dose for this form is 600 mg, with a total maximum dose of 1800 mg over a treatment period of 12 weeks. The second form is a **solution for injection in a pre-filled syringe**, administered subcutaneously. This form has a maximum daily dose of 360 mg and a total maximum dose of 5040 mg over a treatment period of 256 weeks. Both forms are produced by ABBVIE DEUTSCHLAND GMBH & CO. KG and ABBVIE, INC., respectively, and are not pediatric formulations.

The comparator treatment in the study is **Ustekinumab**, also a biologic agent of protein origin. It is available in two forms: a **solution for injection in a pre-filled syringe** and a **concentrate for solution for infusion**. The pre-filled syringe form is administered subcutaneously with a maximum daily dose of 90 mg and a total maximum dose of 450 mg over a 40-week period. The concentrate for infusion is administered intravenously with a maximum daily dose of 520 mg and a total maximum dose of 520 mg over an 8-week period. Both forms are produced by JANSSEN-CILAG INTERNATIONAL NV and are used under study-specific labeling conditions.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen. The trial aims to compare the efficacy and safety of Risankizumab versus Ustekinumab in adult subjects with moderate to severe Crohn's Disease who have failed anti-TNF therapy. The study is designed to provide long-term safety data for Risankizumab, with a continuous treatment extension to ensure uninterrupted care until the treatment becomes commercially available or participants can transition to an open-label extension study.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the evaluation of clinical remission at Week 24, defined as a **Crohn's Disease Activity Index (CDAI)** score of less than 150, and endoscopic remission at Week 48, characterized by a Simple Endoscopic Score for Crohn's Disease (SES-CD) of 4 or less, with at least a 2-point reduction from baseline and no sub-score greater than 1 in any individual variable. These assessments will be conducted by a central reviewer to ensure consistency and accuracy.

Secondary endpoints will focus on the achievement of clinical remission at Week 48, the superiority of risankizumab over ustekinumab in achieving endoscopic response at both Week 24 and Week 48, and the achievement of steroid-free endoscopic and clinical remission at Week 48. The efficacy assessments will be conducted at specified time points, including Week 24 and Week 48, to evaluate the comparative effectiveness of risankizumab versus ustekinumab in adult subjects with moderate to severe Crohn's Disease who have failed anti-TNF therapy.