Efficacy and Safety of Risankizumab in Maintenance and Long-term Extension for Moderately to Severely Active Crohn's Disease: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** and **safety** of **risankizumab** as a maintenance therapy in subjects with moderately to severely active **Crohn's Disease** (CD) who have responded to intravenous risankizumab induction treatment. This is assessed through a randomized, double-blind, placebo-controlled maintenance sub-study (SS1). The clinical relevance of this objective lies in determining the potential of risankizumab to maintain disease remission and improve long-term outcomes for patients with CD.

Additional primary objectives include:

• Evaluating the efficacy and safety of two different dosing regimens for risankizumab (therapeutic drug monitoring vs. clinical assessment for dose escalation) in a randomized, exploratory maintenance sub-study (SS2).
• Assessing the long-term safety of risankizumab in an open-label long-term extension sub-study (SS3) for subjects who completed previous sub-studies or enrolled directly from other related studies.
• Providing continuous treatment with risankizumab in an open-label continuous treatment extension (CTE) to ensure uninterrupted care and further evaluate long-term safety data.

The clinical trial involves a total of **595 participants** diagnosed with **Crohn's Disease**. The study population includes both male and female subjects, encompassing a broad **age range** from adolescents to older adults. Participants were selected based on their completion of prior studies, specifically Study M16-006 or Study M15-991, and their achievement of a clinical response to risankizumab induction treatment. The trial includes individuals who are part of a vulnerable population, indicating a need for careful ethical considerations. Participants are required to provide written informed consent and must be capable of self-administering or having a caregiver administer subcutaneous injections, as per local requirements. The study does not specify particular lifestyle considerations such as diet or physical activity, focusing instead on the medical condition and treatment response. The trial aims to evaluate the efficacy and safety of risankizumab as a maintenance therapy for those with moderately to severely active Crohn's Disease.

The clinical trial is designed to evaluate the efficacy and safety of **risankizumab** in subjects with moderately to severely active **Crohn's Disease**. This is a multicenter, randomized, double-blind, placebo-controlled study with a 52-week maintenance phase and an open-label extension. The trial is divided into several sub-studies, each with specific objectives. Sub-Study 1 (SS1) focuses on the efficacy and safety of risankizumab versus placebo as maintenance therapy. Sub-Study 2 (SS2) explores different dosing regimens for risankizumab. Sub-Study 3 (SS3) is an open-label long-term extension to evaluate the long-term safety and efficacy of risankizumab. Additionally, a Continuous Treatment Extension (CTE) is included to provide ongoing treatment for SS3 completers.

The trial will span from the estimated recruitment start date of April 9, 2018, to the estimated end date of June 9, 2026. Participants are expected to be involved for the duration of the study, with the primary endpoint being the proportion of subjects achieving clinical remission at Week 52. Secondary endpoints include various measures of clinical and endoscopic response, quality of life assessments, and corticosteroid use reduction.

Study visits are structured to ensure comprehensive data collection and participant safety. The inclusion visit, or screening, will confirm eligibility based on criteria such as completion of prior studies and clinical response. Follow-up visits will occur regularly to monitor progress and collect data on primary and secondary endpoints. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any ongoing treatment needs are addressed.

Participant involvement may be terminated early if they do not meet ongoing eligibility criteria, experience adverse events, or withdraw consent. The trial's design ensures rigorous assessment of risankizumab's therapeutic potential in Crohn's Disease, with a focus on maintaining participant safety and data integrity throughout the study duration.

The clinical trial involves the administration of **Risankizumab**, a biologic agent of biotechnological origin, formulated as a **solution for infusion**. The active substance, **risankizumab**, is a protein-based therapeutic. The maximum daily dose is 1200 mg, with a total maximum dose of 7800 mg over a treatment period of up to 52 weeks. The administration route is **intravenous use**, and the product is manufactured by AbbVie Deutschland GmbH & Co. KG. Participant compliance is monitored through scheduled dosing and follow-up visits to ensure adherence to the treatment regimen.

Another formulation of **Risankizumab**, known as ABBV-066, is also used in the trial. This formulation is similarly a **solution for infusion** and is administered intravenously. The maximum daily dose is 1200 mg, with a total maximum dose of 40800 mg over a treatment period of up to 272 weeks. This formulation is also of biological origin and produced by AbbVie Deutschland GmbH & Co. KG. Compliance is monitored through therapeutic drug monitoring and clinical assessments for dose adjustments.

Additionally, **Risankizumab** is available as a **solution for injection in a pre-filled syringe** for **subcutaneous use**. The maximum daily dose for this formulation is 360 mg, with a total maximum dose of 16920 mg over a treatment period of up to 376 weeks. This formulation is produced by AbbVie, Inc., and participant adherence is ensured through regular monitoring and follow-up.

The trial includes a **placebo** for **Risankizumab** in two forms: a **solution for injection in a pre-filled syringe** and a **solution for infusion**. These placebos are used to maintain the double-blind nature of the study, ensuring unbiased assessment of the efficacy and safety of **Risankizumab**. The placebo administration follows the same routes and schedules as the active treatments, with compliance monitored similarly to the active treatment groups.

The efficacy of **Risankizumab** in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the proportion of subjects achieving clinical remission and endoscopic response at Week 52 in Sub-Study 1 (SS1), as well as the evaluation of long-term safety in Sub-Study 3 (SS3). Secondary endpoints encompass a range of measures, such as the proportion of participants with clinical remission per the Crohn's Disease Activity Index (CDAI) at Week 52, the proportion of subjects with ulcer-free endoscopy, and the mean change in the Inflammatory Bowel Disease Questionnaire (IBDQ) total score from baseline of induction to Week 52.

Additional secondary endpoints include the mean change in the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue score at Week 52, the proportion of subjects who discontinued corticosteroid use for 90 days and achieved clinical remission, and the proportion of subjects with enhanced clinical response and deep remission at Week 52. The study will also evaluate the exposure-adjusted occurrence of Crohn's Disease-related hospitalizations from Week 0 through Week 52 and the change from baseline in the Short Form-36 (SF-36) Physical Component Summary score at Week 52.

These efficacy parameters will be measured and collected at specified timepoints, primarily at Week 52, using validated scales and patient-reported outcomes. The analysis will focus on comparing the outcomes between the treatment and placebo groups, as well as assessing the long-term efficacy and safety of Risankizumab in subjects with Crohn's Disease.