Evaluation of Vedolizumab Intravenous Maintenance Therapy Efficacy and Safety in Pediatric Patients with Moderate to Severe Crohn's Disease

The primary objective of this study is to evaluate the **efficacy** of two different dose regimens of vedolizumab administered intravenously in pediatric subjects with moderately to severely active Crohn's disease (CD) during maintenance therapy. This evaluation is based on clinical and endoscopic assessments at Week 54. The clinical relevance of this objective lies in determining the optimal dosing strategy for maintaining disease remission in this patient population, which could significantly impact treatment protocols and patient outcomes.

Secondary objectives include: - Evaluating the efficacy of high and low doses of vedolizumab IV as measured by clinical and endoscopic remission at Weeks 14 and 54. - Assessing the efficacy of these doses in achieving sustained clinical and endoscopic remission, as well as sustained clinical response and endoscopic remission at Week 54. - Evaluating the effect of vedolizumab on achieving corticosteroid-free remission at Week 54. - Assessing the clinical response and clinical remission over time up to Week 54. - Evaluating vedolizumab pharmacokinetics (PK) in pediatric subjects with moderately to severely active CD after IV administration. - Evaluating safety in pediatric subjects on maintenance therapy up to Week 54. - Assessing the immunogenicity of vedolizumab in pediatric subjects with moderately to severely active CD treated with vedolizumab IV. - Evaluating the effect of vedolizumab on patterns of growth and pubertal development in pediatric subjects with moderately to severely active CD during their participation in the study.

The clinical trial involves a total of **40 participants** diagnosed with **moderately to severely active Crohn's disease**. The study population comprises pediatric subjects aged **2 to 17 years**, inclusive, with a minimum weight of 10 kg at the time of screening and enrollment. Both **male and female** participants are included, and the trial specifically targets a vulnerable population due to the age range and health condition. Participants were selected based on their diagnosis of Crohn's disease at least one month prior to screening, with disease activity defined by a Pediatric Crohn's Disease Activity Index (PCDAI) greater than 30 and a Simple Endoscopic Score for Crohn's Disease (SES-CD) greater than 6, or greater than 4 if the disease is confined to the terminal ileum. The trial 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 countrywide accepted schedule of childhood vaccines. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed as a **randomized**, **double-blind**, Phase 3 study to evaluate the efficacy and safety of **vedolizumab** intravenous as maintenance therapy in pediatric subjects with moderately to severely active **Crohn's disease**. The trial aims to assess the efficacy of two different dose regimens of vedolizumab IV during maintenance therapy, based on clinical and endoscopic assessments at Week 54. The study is expected to run from January 31, 2022, to November 27, 2026, with participant involvement lasting up to 54 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, weight, and disease severity. Subjects must be aged 2 to 17 years, weigh at least 10 kg, and have a diagnosis of Crohn's disease at least one month prior to screening. The screening will also ensure that subjects have failed or been intolerant to previous treatments, such as corticosteroids or TNF-α antagonist therapy. Following the screening, eligible participants will enter the maintenance phase, where they will receive vedolizumab IV.

Throughout the trial, participants will attend follow-up visits at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 to monitor clinical and endoscopic responses, as well as safety assessments. The primary endpoints include achieving clinical remission and endoscopic response at Week 54. Secondary endpoints involve clinical and endoscopic remission at various time points, sustained remission, and corticosteroid-free remission. Safety assessments will include monitoring adverse events, serious adverse events, and specific conditions such as opportunistic infections and liver injury.

The end-of-study visit will occur at Week 54, where final assessments will be conducted to evaluate the long-term efficacy and safety of the treatment. Participants may be terminated early from the study if they experience significant adverse events, fail to adhere to the study protocol, or withdraw consent. The trial is not categorized as low intervention and is considered a Category 2 trial under the regulation, focusing on the efficacy and safety of the investigational product.

The clinical trial involves the administration of **PREDNISONE**, a corticosteroid, as an auxiliary treatment. **PREDNISONE** is provided in the form of tablets and is administered orally. The maximum daily dose is 40 mg, with a total maximum dose of 5075 mg over a treatment period of up to 26 weeks. This formulation is specifically designed for pediatric use, ensuring appropriate dosing and safety for younger participants. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

Another auxiliary treatment used in the study is **BUDESONIDE**, also a corticosteroid, which is administered in capsule form. The route of administration is oral, with a maximum daily dose of 9 mg and a total maximum dose of 504 mg over a treatment period of up to 8 weeks. Unlike **PREDNISONE**, **BUDESONIDE** is not formulated specifically for pediatric use. Participant compliance with the dosing schedule is closely monitored to maintain the integrity of the trial data.

The primary experimental medication in this trial is **VEDOLIZUMAB**, marketed as Entyvio, which is a biologic agent used as a test treatment. **VEDOLIZUMAB** is provided as a powder for concentrate for solution for infusion and is administered intravenously. The maximum daily dose is 300 mg, with a total maximum dose of 113.4 g over a treatment period of up to 54 weeks. This medication is not formulated specifically for pediatric use. The administration of **VEDOLIZUMAB** is conducted under controlled conditions to ensure accurate dosing and participant safety. Compliance with the infusion schedule is rigorously monitored to ensure the reliability of the trial outcomes.

The efficacy of vedolizumab intravenous as maintenance therapy in pediatric subjects with moderately to severely active Crohn's Disease will be assessed using both clinical and endoscopic parameters. The primary endpoints include clinical remission, defined as a Pediatric Crohn's Disease Activity Index (PCDAI) score of ≤10 at Week 54, and endoscopic response, characterized by at least a 50% reduction in the Simple Endoscopic Score for Crohn's Disease (SES-CD) from baseline at Week 54.

Secondary endpoints will evaluate clinical and endoscopic remission at Weeks 14 and 54, sustained clinical and endoscopic remission at Week 54, and corticosteroid-free remission at Week 54. Additional assessments include serum trough concentrations of vedolizumab, positive antivedolizumab antibody titers, and sustained clinical response at Weeks 14 and 54. Clinical remission and response will also be measured at multiple timepoints, including Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54, using the PCDAI score.

Data collection will involve validated scales and laboratory tests to ensure accurate measurement of these endpoints. The schedule for efficacy assessments is structured to capture both short-term and long-term outcomes, providing a comprehensive evaluation of vedolizumab's efficacy in this patient population.