A Phase 3b Extension Study to Evaluate the Long-Term Safety of Vedolizumab Subcutaneous in Pediatric Subjects With Ulcerative Colitis or Crohn’s Disease

The primary objective is to evaluate the safety profile of long-term subcutaneous vedolizumab treatment in pediatric subjects with ulcerative colitis or Crohn's disease. This objective addresses the clinical need to establish the tolerability and adverse event profile of prolonged subcutaneous administration in the pediatric population with inflammatory bowel disease, which is essential for determining the appropriateness of extended maintenance therapy in this age group.

The secondary objectives include:

• The effect of long-term vedolizumab subcutaneous treatment on time to major inflammatory bowel disease-related events, including hospitalizations, surgeries, and procedures in pediatric subjects with ulcerative colitis or Crohn's disease. This endpoint assesses whether sustained treatment can reduce disease-related morbidity and healthcare utilization.

• Quality of life in subjects aged 9 to 17 years who were treated with vedolizumab subcutaneous using the IMPACT-III questionnaire. This objective evaluates the impact of treatment on patient-reported outcomes and functional status in the adolescent population.

This clinical trial enrolled a total of **34 participants** diagnosed with **Ulcerative Colitis** or **Crohn's Disease**. The study population consisted of **pediatric subjects** aged less than 18 years, including both **male and female** participants. Subjects were selected based on their completion of Week 34 of a previous vedolizumab study (VedolizumabSC-3003), where they achieved **clinical response** and maintained **corticosteroid-free** status for at least the last 4 weeks of that study. For subjects with Ulcerative Colitis, clinical response was defined as a reduction of partial Mayo score of at least 2 points and at least 25% from baseline, including specific decreases in stool frequency and rectal bleeding subscores. For subjects with Crohn's Disease, clinical response was defined as a **PCDAI** score of 30 or less with a reduction of at least 15 points from baseline. Participants or their legally authorized representatives were required to demonstrate capability of understanding and complying with protocol requirements. **Sexually active participants** of childbearing potential were required to use appropriate contraceptive methods throughout the study duration and for 18 weeks after the last dose. The trial also included an observational cohort for subjects who received at least one dose of vedolizumab in the previous study but were not eligible for the treatment cohort.

This Phase 3b extension study evaluates the long-term safety of vedolizumab administered via subcutaneous injection in pediatric subjects with ulcerative colitis or Crohn's disease. The study comprises two cohorts: a treatment cohort and an observational cohort. The treatment cohort is designed as an open-label extension study for subjects who completed Week 34 of the parent study VedolizumabSC-3003, achieved clinical response at that timepoint, and maintained corticosteroid-free status for at least the final four weeks of the parent study. The observational cohort includes subjects who received at least one dose of vedolizumab during the parent study but either terminated early or completed Week 34 without meeting eligibility criteria for the treatment cohort.

The investigational medicinal product is vedolizumab 108 mg solution for injection, available in two formulations: a pre-filled pen and a pre-filled syringe, both administered subcutaneously. The maximum daily dose is 108 mg, with a maximum total dose of 5184 mg over a treatment period of 24 weeks or 24 months depending on the formulation. The active substance, vedolizumab, is a protein of non-chemical origin classified under ATC code L04AG05.

The primary objective for the treatment cohort is to evaluate the safety profile of long-term vedolizumab subcutaneous treatment in pediatric subjects with ulcerative colitis or Crohn's disease. Primary endpoints include the incidence of adverse events, serious adverse events, and adverse events of special interest, specifically infections including opportunistic infections such as progressive multifocal leukoencephalopathy, liver injury, malignancies, injection-related reactions, and systemic reactions including anaphylaxis and hypersensitivity reactions. For the observational cohort, the primary endpoint is the incidence of safety events including serious adverse events, serious infections, malignancies, progressive multifocal leukoencephalopathy, bowel surgery, and delay in growth or pubertal development. Secondary endpoints for the treatment cohort include time to major inflammatory bowel disease-related events such as hospitalizations, surgeries, or procedures from Day 1 of this extension study, and changes from baseline of the parent study in IMPACT-III total and subscale scores for subjects aged 9 to 17 years.

Principal inclusion criteria for the treatment cohort require that subjects are male or female with ulcerative colitis or Crohn's disease aged less than 18 years who completed Week 34 of the parent study with documented clinical response and corticosteroid-free status. Clinical response for subjects with ulcerative colitis is defined as a reduction of partial Mayo score of at least 2 points and at least 25% from baseline, including at least a 1-point decrease in the Mayo stool frequency subscore and at least a 1-point reduction in the rectal bleeding subscore or absolute rectal bleeding subscore of 1 point or less. Clinical response for subjects with Crohn's disease is defined as a Pediatric Crohn's Disease Activity Index of 30 or less with a reduction of at least 15 points from baseline. Subjects or their legally authorized representatives must be capable of understanding and complying with protocol requirements and must provide signed informed consent and any required privacy authorization. Male subjects who are sexually active with female partners of childbearing potential must agree to use barrier contraception throughout the study and for 18 weeks after the last dose. Female subjects of childbearing potential who are sexually active must agree to use highly effective contraception throughout the study and for 18 weeks after the last dose. For the observational cohort, subjects must have received at least one dose of vedolizumab during the parent study and either terminated early or completed Week 34 but were not eligible for the treatment cohort.

The estimated recruitment start date is July 5, 2025, with an estimated study end date of August 9, 2030. The duration of subject participation in the treatment cohort extends from enrollment through the completion of the long-term extension period, with subjects expected to continue treatment as long as they derive clinical benefit and meet continuation criteria. Subjects who reach adult age during the study should be considered for transition to commercial drug if available in their country, particularly if transition to an adult care setting is required by local regulation. Early termination from the study may occur due to withdrawal of consent, loss to follow-up, adverse events requiring discontinuation, lack of efficacy, protocol violations, investigator decision, or other reasons as specified in the protocol.

The experimental medication under investigation is **vedolizumab**, marketed as **Entyvio**, which is administered as a **subcutaneous injection**. The study utilizes two pharmaceutical formulations of vedolizumab: a **solution for injection in pre-filled pen** and a **solution for injection in pre-filled syringe**. Both formulations contain **108 mg** of vedolizumab as the active substance, which is classified as a protein-based biological agent. The pre-filled pen is supplied as an integral combination product consisting of a pre-filled syringe with an autoinjector pen, while the pre-filled syringe formulation is equipped with a needle safety device. The clinical trial material differs from the commercial product in the syringe/pen tip cap composition, with clinical material utilizing FM30 tipcap whereas commercial material uses 4800GS tipcap.

The **maximum daily dose** of vedolizumab administered in this study is **108 mg**, with a **maximum total dose** of **5184 mg** over the course of treatment. The **maximum treatment period** is **24 weeks** for the pre-filled pen formulation and **24 months** for the pre-filled syringe formulation. The **route of administration** for both formulations is via **subcutaneous injection**. The study is designed to evaluate the long-term safety profile of vedolizumab subcutaneous administration in pediatric subjects with **ulcerative colitis** or **Crohn's disease**. Participant compliance monitoring will be conducted throughout the treatment period to ensure adherence to the prescribed dosing schedule and to assess the safety outcomes associated with prolonged vedolizumab exposure in the pediatric population.

Efficacy will be assessed in the treatment cohort through evaluation of time to major inflammatory bowel disease-related events, including hospitalizations, surgeries, or procedures, measured from Day 1 of the study. Additionally, changes from baseline in IMPACT-III total and subscale scores will be evaluated for subjects aged 9 to 17 years. The baseline for these assessments is defined as the baseline from the preceding Study VedolizumabSC-3003. Entry into the treatment cohort requires subjects to have achieved clinical response at Week 34 of the parent study and to have been corticosteroid-free for at least the last 4 weeks. For subjects with ulcerative colitis, clinical response is defined as a reduction of partial Mayo score of at least 2 points and at least 25% from baseline, including at least a 1-point decrease in the Mayo stool frequency subscore and at least a 1-point reduction in the rectal bleeding subscore or an absolute rectal bleeding subscore of 1 point or less. For subjects with Crohn's disease, clinical response is defined as a Pediatric Crohn's Disease Activity Index of 30 or less with a reduction in the index of at least 15 points from baseline.