Evaluation of Vedolizumab Intravenous as Maintenance Therapy in Pediatric Patients with Moderately to Severely Active Ulcerative Colitis

The primary objective of this study is to evaluate the **efficacy** of two different dose regimens of vedolizumab intravenous (IV) in pediatric subjects with moderately to severely active **ulcerative colitis** (UC) during maintenance therapy, based on clinical remission at Week 54. This is clinically relevant as achieving and maintaining remission is a critical goal in the management of UC, particularly in pediatric populations where long-term disease control can significantly impact growth and development.

Secondary objectives include:

• The efficacy of high and low doses of vedolizumab IV in pediatric subjects with moderately to severely active UC, based on clinical remission at Week 14.
• The efficacy of high and low doses of vedolizumab IV as measured by sustained clinical remission at Weeks 14 and 54.
• The efficacy of high and low doses of vedolizumab IV as measured by sustained clinical response at Weeks 14 and 54.
• The efficacy of high and low doses of vedolizumab IV as measured by sustained endoscopic remission at Weeks 14 and 54.
• The efficacy of high and low doses of vedolizumab IV as measured by endoscopic response at Weeks 14 and 54.
• The effect of high and low doses of vedolizumab IV on achieving corticosteroid-free remission at Week 54.
• The effect of high and low doses of vedolizumab IV on clinical response over time up to Week 54.
• The efficacy of high and low doses of vedolizumab IV as measured by clinical remission over time up to Week 54.
• Vedolizumab pharmacokinetics (PK) in pediatric subjects with moderately to severely active UC after IV administration.
• Safety in pediatric subjects on maintenance therapy up to Week 54.
• The immunogenicity of vedolizumab in pediatric subjects with moderately to severely active UC treated with vedolizumab IV.
• The effect of vedolizumab on patterns of growth and pubertal development in pediatric subjects with moderately to severely active UC during their participation in the study.

The clinical trial involves a total of **8 participants** diagnosed with **moderately to severely active Ulcerative Colitis (UC)**. The study population consists of pediatric subjects aged **2 to 17 years**, inclusive, with both **male and female** participants. The trial population was selected based on specific criteria, including a diagnosis of UC at least one month prior to screening and a modified Mayo score indicating moderate to severe disease activity. Participants are required to weigh at least 10 kg and have evidence of UC extending beyond the rectum. The study includes subjects who have previously failed, lost response to, or been intolerant to treatments such as corticosteroids, immunomodulators, or TNF-α antagonist therapy. Additionally, participants must have up-to-date vaccinations according to the accepted schedule of childhood vaccines in their country. The trial focuses on evaluating the efficacy of vedolizumab IV in maintaining clinical remission at Week 54.

The clinical trial is designed as a **randomized, double-blind, controlled** study to evaluate the efficacy and safety of **vedolizumab** intravenous as maintenance therapy in pediatric subjects with moderately to severely active **ulcerative colitis**. The trial aims to assess two different dose regimens of vedolizumab, with the primary endpoint being clinical remission at Week 54. The study is expected to last until August 2025, with participant recruitment having commenced in May 2021. The trial involves multiple study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, weight, and disease severity. Participants will then enter the maintenance phase, with follow-up visits scheduled at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 to monitor clinical response and remission. The end-of-study visit will occur at Week 54, where the primary and secondary endpoints will be evaluated. The expected length of participant involvement is approximately 54 weeks. Conditions that may lead to early termination from the study include failure to meet the inclusion criteria, adverse events, or withdrawal of consent. The trial will ensure that all safety assessments, including adverse events and serious adverse events, are thoroughly documented throughout the study duration.

The clinical trial involves the administration of two primary treatments. The first treatment is **PREDNISONE**, a corticosteroid provided in the form of a tablet. The active substance, prednisone, is of chemical origin. The maximum daily dose of prednisone is 40 mg, with a total maximum dose of 5075 mg over the treatment period. The administration route for prednisone is intravenous, and the treatment duration is up to 26 weeks. Participant compliance with the dosing schedule will be monitored throughout the study.

The second treatment is **VEDOLIZUMAB**, marketed under the name Entyvio, which is provided as a 300 mg powder for concentrate for solution for infusion. Vedolizumab is a protein-based medication, specifically classified as "Protein - Other." The maximum daily dose is 300 mg, with a total maximum dose of 113.4 g over the treatment period. The administration route is intravenous, and the treatment duration extends up to 54 weeks. Vedolizumab is not a pediatric formulation, and its administration will be closely monitored to ensure adherence to the dosing schedule.

In this study, prednisone serves as an auxiliary treatment, while vedolizumab is the test treatment. The trial aims to evaluate the efficacy of vedolizumab as maintenance therapy in pediatric subjects with moderately to severely active ulcerative colitis. The study will assess clinical remission at Week 54, following an initial open-label vedolizumab intravenous therapy phase. Compliance with the treatment regimen will be systematically monitored to ensure the integrity of the trial results.

The efficacy of vedolizumab intravenous as maintenance therapy in pediatric subjects with moderately to severely active **Ulcerative Colitis** (UC) will be assessed through a series of predefined endpoints. The primary endpoint is clinical remission at Week 54, defined by a modified Mayo score. This includes a stool frequency subscore of 0 to 1 with a decrease of 1 or more from baseline, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 to 1, where a score of 1 does not include friability.

Secondary endpoints include clinical remission at Week 14, sustained clinical remission at Week 54, and sustained endoscopic remission at Weeks 14 and 54, defined as a Mayo Endoscopic Subscore (MES) of ≤1 point. Endoscopic response is evaluated by a decrease in MES of ≥1 point at Weeks 14 and 54. Corticosteroid-free clinical remission at Week 54 is also assessed, requiring subjects to meet the primary endpoint criteria and be off corticosteroids for at least 12 weeks prior to and at Week 54. Additional secondary endpoints include clinical remission based on the complete Mayo score at Week 54, serum trough concentrations of vedolizumab over time, and the presence of positive anti-vedolizumab antibodies (AVA) and neutralizing AVA during the study.

Clinical response is measured at multiple timepoints, including Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54, defined by a reduction of ≥2 points and ≥25% from the baseline partial Mayo score, with a ≥1 point decrease in the stool frequency subscore and a ≥1 point reduction in the rectal bleeding subscore or an absolute rectal bleeding subscore of ≤1 point. Safety assessments will also be conducted, including descriptions of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs), such as opportunistic infections, liver injury, malignancies, infusion-related reactions, and hypersensitivity. Changes from baseline in weight gain, linear growth z-score, and Tanner stage at Week 54 will be evaluated as part of the efficacy assessment.