Evaluation of Pharmacokinetics, Efficacy, and Safety of Risankizumab in Pediatric Patients with Moderate to Severe Ulcerative Colitis

The primary objective of this Phase 3, multi-center study is to evaluate the **pharmacokinetics** (PK), efficacy, and safety of **risankizumab** in pediatric subjects aged 2 to less than 18 years with moderately to severely active **ulcerative colitis**. This is clinically relevant as it aims to determine the appropriate dosing, therapeutic effectiveness, and safety profile of risankizumab in a pediatric population, which is crucial for managing this chronic inflammatory bowel disease in younger patients. No secondary objectives are specified in the provided data.

The clinical trial involves a total of **87 participants** diagnosed with **ulcerative colitis**. The study population comprises pediatric subjects aged 2 to less than 18 years, including both male and female participants. The trial specifically targets individuals with moderately to severely active ulcerative colitis, as indicated by a modified Mayo Score of 5 to 9 points and an endoscopic subscore of 2 to 3. Participants were selected based on their demonstrated intolerance or inadequate response to certain drug categories, including aminosalicylates, corticosteroids, immunomodulators, and biologic therapies. All subjects have a documented history of ulcerative colitis for at least three months prior to the baseline, confirmed by colonoscopy, with exclusion of current infection, colonic dysplasia, and malignancy. The trial population includes a vulnerable group, reflecting the pediatric nature of the study. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the **pharmacokinetics**, efficacy, and safety of **risankizumab** in pediatric subjects aged 2 to less than 18 years with moderately to severely active **ulcerative colitis**. This is a Phase 3, multi-center study that includes open-label induction, randomized double-blind maintenance, and open-label long-term extension periods. The trial is structured to ensure rigorous assessment through a randomized, double-blind, controlled methodology. The estimated duration of the trial extends until July 2034, with recruitment anticipated to commence in September 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a modified Mayo Score of 5 to 9 points and a documented history of ulcerative colitis for at least three months. The screening will include a colonoscopy to exclude current infection, colonic dysplasia, and malignancy. Following the screening, participants will enter the induction phase, where they will receive open-label treatment. Subsequent visits will occur during the maintenance phase, which is randomized and double-blind, to assess primary endpoints such as maximum observed serum concentration and time to maximum serum concentration. The study will also evaluate secondary endpoints, including clinical remission and response at various intervals, such as Weeks 12 and 64.

The expected length of participant involvement is up to 248 weeks, depending on the cohort and response to treatment. Conditions that may lead to early termination from the study include adverse events, withdrawal of consent, or failure to meet ongoing eligibility criteria. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any post-study care is arranged. The trial's design and procedures are meticulously planned to ensure the collection of comprehensive data on the safety and efficacy of risankizumab in the target population.

The clinical trial involves the administration of **Risankizumab**, a biologic agent classified as a protein of other origin. The pharmaceutical form of Risankizumab is a solution for injection in a pre-filled syringe. It is administered subcutaneously. The dosing schedule is not explicitly detailed in the provided data, but the maximum treatment period is specified as 248 days. The trial aims to evaluate the pharmacokinetics, efficacy, and safety of Risankizumab in pediatric subjects aged 2 to less than 18 years with moderately to severely active ulcerative colitis.

In addition to the active treatment, a **placebo** is utilized in the study. The placebo is referred to as "risankizumab placebo" and serves as a comparator to assess the efficacy and safety of the active treatment. The specific pharmaceutical form, route, and frequency of administration for the placebo are not detailed in the provided data. The placebo is used during the randomized double-blind maintenance phase of the trial to ensure the validity of the study results.

Another formulation of Risankizumab, identified as **ABBV-066**, is also included in the trial. This formulation is similarly a solution for injection in a pre-filled syringe and is administered subcutaneously. The maximum treatment period for this formulation is also 248 days. The trial includes an open-label induction phase, a randomized double-blind maintenance phase, and an open-label long-term extension period to comprehensively assess the treatment's impact on the target population.

Additionally, the trial involves the administration of **ABBV-066 / Risankizumab** as a solution for infusion. This formulation is administered intravenously, with a maximum treatment period of 8 days. The inclusion of this formulation allows for the evaluation of different administration routes and their respective impacts on the pharmacokinetics and efficacy of the treatment in the pediatric population with ulcerative colitis.

The efficacy of **risankizumab** in the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints include the pharmacokinetic parameters such as Maximum Observed Serum Concentration (Cmax), Time to Maximum Serum Concentration (Tmax), and Area Under the Serum Concentration-Time Curve Over the Dosing Interval (AUCtau) for PK Lead-in Cohort 1 and Cohort 2. Additionally, the achievement of clinical remission per Modified Mayo Score (mMS) at Week 64 among Week 12 clinical responders per mMS is a primary endpoint for Expansion Cohort 3.

Secondary endpoints focus on clinical outcomes and include the achievement of clinical remission and response per mMS at various time points, such as Week 12 and Week 64, for both PK Lead-In Cohorts and Expansion Cohort 3. Endoscopic improvement and symptomatic response per partial mMS at Week 12 are also evaluated. Furthermore, the ability to discontinue corticosteroids prior to Week 64 and achieve clinical remission per mMS among Week 12 responders is assessed. These endpoints are measured using the Modified Mayo Score, a validated scale for evaluating disease activity in ulcerative colitis.