A Multicenter, Double-Blind, Randomized Study Comparing the Safety and Efficacy of Vedolizumab Versus Infliximab in Pediatric Ulcerative Colitis Patients

The primary objective of this study is to assess the **safety** of vedolizumab induction therapy compared to standard infliximab therapy in pediatric patients with **ulcerative colitis**. This evaluation is clinically relevant as it aims to determine the risk profile of vedolizumab, a drug not yet registered for pediatric use, in comparison to the established treatment with infliximab. Understanding the safety of these therapies is crucial for optimizing treatment strategies in this vulnerable population.

The secondary objective is to evaluate the **effectiveness** of vedolizumab relative to infliximab. This aspect of the study is important for determining the therapeutic potential and clinical benefits of vedolizumab in managing ulcerative colitis in children aged 6-17 years.

The clinical trial involves **participants** diagnosed with **ulcerative colitis**, specifically targeting a pediatric population aged 6 to 17 years. Both male and female subjects are included in the study, with no vulnerable populations being selected. The trial population was chosen based on specific criteria, including a diagnosis of moderate or severe ulcerative colitis, as defined by a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of at least 30 points, and a history of inadequate response, loss of response, or intolerance to standard treatments such as corticosteroids or immunomodulatory drugs. Participants are required to have a proximal location of ulcerative colitis not limited to rectal inflammation and a Mayo Endoscopic Scale score of at least 1 point. Additionally, subjects must have current immunizations in line with the Polish immunization program, including vaccinations with live vaccines. The total number of participants is not provided, as the sponsor did not give this information.

The clinical trial is designed to evaluate the **safety** and effectiveness of vedolizumab induction therapy compared to standard infliximab therapy in pediatric patients with **ulcerative colitis**. This is a multicenter, double-blind, randomized study involving participants aged 6 to 17 years. The trial will be conducted over a period of approximately four years, with an estimated end date of November 30, 2028. Participants will be randomly assigned to receive either vedolizumab or infliximab, both administered intravenously as a **solution for infusion**. The primary endpoint is the safety of biological treatment, defined by the number of drug-related adverse events. Secondary endpoints include clinical response and remission as measured by the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Mayo endoscopic score.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility criteria are assessed. Participants must have a moderate or severe form of ulcerative colitis, defined as a minimum of 30 points in the PUCAI, and must have been diagnosed at least one month prior to the screening visit. Follow-up visits will occur at regular intervals to monitor the participants' response to treatment and to assess any adverse events. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the overall safety and effectiveness of the treatments.

The expected length of participant involvement is up to 20 weeks, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include the occurrence of severe adverse events, withdrawal of consent, or non-compliance with the study protocol. Participants will be closely monitored throughout the trial to ensure their safety and well-being. The trial is not classified as low intervention and is categorized as a Phase 4 study, focusing on the post-marketing assessment of the treatments' safety and effectiveness in a pediatric population.

The clinical trial involves the administration of **vedolizumab**, marketed under the name Entyvio, as the experimental medication. Entyvio is provided in the form of a **powder for concentrate for solution for infusion**. Each vial contains 300 mg of vedolizumab, a monoclonal antibody classified under the ATC code L04AA33. The medication is administered via **infusion**. The maximum daily dose is 300 mg, with a total maximum dose of 1200 mg over a treatment period of 20 weeks. Vedolizumab is a protein-based therapeutic agent, specifically designed to target and modulate the immune response in patients with **ulcerative colitis**. Compliance with the dosing schedule is monitored through regular assessments and infusion records.

The comparator treatment in this study is **infliximab**, which is also administered as a **powder for concentrate for solution for infusion**. Infliximab is a chimeric monoclonal antibody used as a standard-of-care therapy for ulcerative colitis. The dosing regimen for infliximab is based on body weight, with a maximum daily dose of 5 mg/kg and a total maximum dose of 20 mg/kg over the same 20-week treatment period. The administration route is via infusion, similar to vedolizumab. Participant compliance with infliximab administration is tracked through infusion logs and periodic evaluations to ensure adherence to the prescribed dosing schedule.

Efficacy in the clinical trial titled "Assessment of the safety and effectiveness of vedolizumab induction therapy compared to standard infliximab therapy in pediatric patients with **ulcerative colitis** 'VEDI-UC'" will be assessed using several endpoints. The primary endpoint focuses on the safety of biological treatment with vedolizumab and infliximab, defined by the number of drug-related adverse events (AEs). Secondary endpoints include various measures of clinical response and remission. These are quantified by changes in the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Mayo endoscopic score. Specifically, clinical response is defined as a decrease in PUCAI value by a minimum of 20 points, while clinical remission is indicated by a PUCAI value of less than 10 points. Mucosal remission is assessed with a Mayo endoscopic score of 0. Additionally, clinical response and remission are evaluated using both the total and partial Mayo scales, with specific criteria for point reductions and score thresholds.