Phase 3 Evaluation of Vedolizumab Subcutaneous Pharmacokinetics, Safety, and Immunogenicity in Pediatric Patients with Moderate to Severe Ulcerative Colitis or Crohn's Disease

The primary objective of this study is to assess the **pharmacokinetics** of vedolizumab administered subcutaneously in pediatric subjects with moderately to severely active **ulcerative colitis** or **Crohn's disease** at steady state. This evaluation is clinically relevant as it aims to determine the drug's absorption, distribution, metabolism, and excretion in this specific patient population, which is crucial for optimizing therapeutic strategies and ensuring effective disease management.

The clinical trial involves a total of **38 participants** diagnosed with **Active Ulcerative Colitis** or **Crohn's Disease**. The study population includes both male and female pediatric subjects, classified under age range category code 2, indicating a specific pediatric age group. Participants were selected based on their diagnosis of moderately to severely active disease, with specific criteria for **Ulcerative Colitis** and **Crohn's Disease** activity indices. The trial population includes individuals who have previously failed, lost response to, or been intolerant to certain treatments such as corticosteroids, immunomodulators, and TNF-α antagonist therapy. Participants are required to weigh at least 10 kg at the time of screening and enrollment. The study also considers lifestyle factors such as up-to-date vaccinations according to the countrywide accepted schedule of childhood vaccines. The trial includes a vulnerable population, ensuring careful consideration of ethical standards in the study design.

The clinical trial is designed as an open-label, Phase 3 study to evaluate the pharmacokinetics, safety, and immunogenicity of **vedolizumab** administered subcutaneously in pediatric subjects with moderately to severely active **ulcerative colitis** or **Crohn's disease**. The trial will involve participants who have achieved a clinical response following open-label vedolizumab intravenous therapy. The study is expected to commence recruitment on October 31, 2024, and conclude by June 30, 2027. Participants will be involved in the study for a maximum treatment period of 20 weeks, with the primary objective being the assessment of the pharmacokinetics of vedolizumab at steady state.

The trial will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor the participants' response to the treatment, and an end-of-study visit to assess the overall outcomes. The inclusion criteria require participants to weigh at least 10 kg and have a confirmed diagnosis of ulcerative colitis or Crohn's disease for at least one month prior to screening. Participants must have failed, lost response to, or been intolerant to previous treatments such as corticosteroids, immunomodulators, or TNF-α antagonist therapy. The study will exclude participants who do not meet these criteria or have other disqualifying conditions.

The primary endpoints of the study include the steady-state median observed plasma concentration and the average serum concentration of vedolizumab at Week 34. Secondary endpoints will assess the percentage of participants with positive antivedolizumab antibodies and neutralizing antibodies up to 18 weeks after the last dose of the study drug. Participants may be withdrawn from the study if they experience adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The study will utilize a solution for injection in a pre-filled syringe for subcutaneous use, with a maximum daily dose of 108 mg and a total dose of 1080 mg over the treatment period.

The clinical trial involves the administration of two formulations of **vedolizumab**, a monoclonal antibody used in the treatment of moderately to severely active ulcerative colitis and Crohn's disease. The first formulation is **Entyvio 300 mg powder for concentrate for solution for infusion**. This pharmaceutical form is a powder that is reconstituted to create a solution for intravenous infusion. The maximum daily dose is 300 mg, with a total maximum dose of 900 mg over a treatment period of up to 6 weeks. The administration route is via intravenous infusion, which requires careful preparation and monitoring to ensure proper dosing and participant compliance.

The second formulation used in the trial is **Entyvio 108 mg solution for injection in pre-filled syringe**. This formulation is designed for subcutaneous use and is provided in a pre-filled syringe equipped with a needle safety device. The maximum daily dose for this formulation is 108 mg, with a total maximum dose of 1080 mg over a treatment period of up to 20 weeks. The subcutaneous administration allows for a more convenient dosing schedule, potentially improving participant compliance. The pre-filled syringe is an integral combination product, ensuring ease of use and safety during administration.

Both formulations of vedolizumab are manufactured by Takeda Pharma A/S and are not classified as pediatric formulations. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. Participant compliance is monitored through regular assessments and adherence checks to ensure the accurate administration of the investigational products. The trial aims to evaluate the pharmacokinetics, safety, and immunogenicity of vedolizumab in pediatric subjects who have achieved a clinical response following open-label vedolizumab intravenous therapy.

Efficacy in this clinical trial will be assessed through primary and secondary endpoints. The primary endpoints include the **Ctrough,ss**, which is the steady-state median observed plasma concentration at the end of a dosing interval for vedolizumab at Week 34, and the **Cavg,ss**, which is the average serum concentration at steady-state for vedolizumab at Week 34. These measurements will be taken at multiple time points prior to Week 34, with a specific focus on pre-dose levels at Week 34.

Secondary endpoints will evaluate the immunogenicity of vedolizumab by measuring the percentage of participants with positive antivedolizumab antibodies (AVA) and positive neutralizing AVA. These assessments will be conducted from baseline up to 18 weeks after the last dose of the study drug, extending up to Week 50. The trial aims to provide comprehensive data on the pharmacokinetics, safety, and immunogenicity of vedolizumab in pediatric subjects with moderately to severely active ulcerative colitis or Crohn's disease who have achieved a clinical response following open-label vedolizumab intravenous therapy.