Comparative Efficacy and Safety of Risankizumab Versus Vedolizumab in Adult Patients With Moderate to Severe Ulcerative Colitis Naïve to Targeted Therapies

The primary objective of this study is to compare the **efficacy** and **safety** of **risankizumab** versus **vedolizumab** over a 48-week period for the treatment of adult subjects with moderate to severe **Ulcerative Colitis** who are naïve to targeted therapies. This comparison is clinically relevant as it aims to determine the most effective treatment option for patients who have not previously been exposed to targeted therapies, potentially influencing future treatment guidelines and improving patient outcomes in this population.

The clinical trial involves a total of **280 participants** diagnosed with **Ulcerative Colitis**. The study population comprises both male and female adults, aged between 18 and 64 years, who have been diagnosed with moderate to severe Ulcerative Colitis for at least three months prior to the baseline. Participants were selected based on their active disease status, characterized by a modified Mayo Score of 5 to 9 points and an endoscopic subscore of 2 to 3, as confirmed by a central reader. The trial specifically includes individuals who have shown intolerance or inadequate response to one or more categories of drugs, such as aminosalicylates, oral locally acting steroids, systemic steroids like prednisone, and immunomodulators. The study does not involve a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.

The clinical trial is a **Phase 3b**, multicenter, randomized, open-label study designed to compare the efficacy and safety of **risankizumab** versus **vedolizumab** in adult subjects with moderate to severe **ulcerative colitis** who are naïve to targeted therapies. The trial aims to evaluate the superiority of risankizumab over vedolizumab in achieving endoscopic improvement at Week 48, defined as a centrally read endoscopy subscore of 0 or 1. Additionally, the study will assess the non-inferiority and potential superiority of risankizumab in achieving clinical remission per modified Mayo Score (mMS) at Week 48.

The trial will span an estimated duration from July 2025 to October 2028, with a maximum treatment period of 48 weeks for each participant. Participants will be randomly assigned to receive either risankizumab or vedolizumab, administered via **intravenous infusion** or **subcutaneous injection** as per the respective product's pharmaceutical form. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as a confirmed diagnosis of ulcerative colitis and a modified Mayo Score of 5 to 9, followed by regular follow-up visits to monitor treatment response and safety. The end-of-study visit will occur at the conclusion of the 48-week treatment period.

Participant involvement is expected to last for the entire 48-week treatment period unless early termination is warranted. Conditions that may lead to early termination include significant adverse events, withdrawal of consent, or any other medical reasons deemed necessary by the investigator. The trial will adhere to rigorous methodological standards to ensure the reliability and validity of the results, contributing valuable insights into the comparative effectiveness of these treatments for ulcerative colitis.

The clinical trial involves the administration of **Risankizumab**, marketed as ABBV-066, which is a **solution for infusion**. This experimental medication is of biological/biotechnological origin and is administered via **intravenous infusion**. The dosing schedule is designed for a maximum treatment period of 48 weeks. The specific dosage and frequency of administration are determined based on the study protocol, ensuring adherence to safety and efficacy standards. Participant compliance is monitored through regular assessments and documentation of infusion sessions.

Additionally, the trial includes a comparator treatment, **Vedolizumab**, marketed as Entyvio. This medication is provided as a **powder for concentrate for solution for infusion** and is also administered via **intravenous infusion**. Vedolizumab is of chemical origin and serves as a standard-of-care therapy in this study. The treatment duration for Vedolizumab is aligned with the experimental medication, spanning up to 48 weeks. Compliance with the dosing schedule is closely monitored to ensure the integrity of the comparative analysis.

Another formulation of **Risankizumab**, also referred to as ABBV-066, is included in the study as a **solution for injection in a pre-filled syringe**. This formulation is administered via **subcutaneous injection**. The administration schedule and monitoring procedures are consistent with the intravenous formulation, maintaining a maximum treatment period of 48 weeks. The study protocol outlines specific measures for tracking participant adherence to the injection regimen, ensuring accurate data collection and analysis.

The efficacy of the clinical trial will be assessed by comparing the performance of **risankizumab** versus vedolizumab in adult subjects with moderate to severe Ulcerative Colitis who are naïve to targeted therapies. The primary endpoint for evaluating efficacy is the achievement of endoscopic improvement at Week 48, defined as a centrally read endoscopy subscore of 0 or 1, with a score of 1 modified to exclude friability. This endpoint aims to demonstrate the superiority of **risankizumab** over vedolizumab.

Secondary endpoints include the achievement of clinical remission per modified Mayo Score (mMS) at Week 48. Clinical remission is defined as a stool frequency subscore (SFS) of ≤ 1, not greater than Baseline, a rectal bleeding subscore (RBS) of 0, and a centrally read endoscopy subscore of 0 or 1, with a score of 1 modified to exclude friability. The analysis will first test for non-inferiority of **risankizumab** compared to vedolizumab, followed by a test for superiority. These assessments will be conducted at the 48-week mark to determine the efficacy of the treatments in achieving the desired clinical outcomes.