Evaluation of Vedolizumab Intravenous Efficacy and Safety in Pediatric Patients with Active Chronic Pouchitis: A Phase 3 Open-Label Study

The primary objective of this study is to assess the **efficacy** of vedolizumab IV in pediatric subjects with active chronic pouchitis, specifically by evaluating the proportion of subjects who achieve clinical remission at Week 14. This is clinically relevant as achieving clinical remission is a critical endpoint in the management of chronic pouchitis, potentially improving patient outcomes and quality of life.

Secondary objectives include evaluating the efficacy of vedolizumab IV by: - The proportion of subjects achieving clinical remission at Week 34. - The proportion of subjects achieving Pouchitis Disease Activity Index (PDAI) remission evaluated separately at Week 14 and Week 34. - The proportion of subjects achieving clinical response evaluated separately at Week 14 and Week 34. - Change from baseline in modified PDAI (mPDAI) score total at Week 14 and Week 34. - Change from baseline in PDAI total score and PDAI clinical symptoms, endoscopic, and histology subscores at Week 14 and Week 34. - Change from baseline in age-appropriate health-related quality of life measured by EQ-5D-Y Proxy Version 1.1 at Week 14 and Week 34.

The clinical trial involves a total of **2 participants** diagnosed with **active chronic pouchitis**. The study population comprises pediatric subjects aged **2 to 17 years**, inclusive, and includes both male and female participants. The participants were selected based on specific criteria, including a history of proctocolectomy and ileal pouch-anal anastomosis (IPAA) completed at least one year prior to the screening visit. The trial population is characterized by individuals who have experienced at least one previous episode of pouchitis within the year before screening, with symptoms persisting for a minimum of four weeks and treated with at least two weeks of antibiotic or other prescription therapy. Additionally, participants may have had an inadequate response to, or intolerance of, antibiotic therapy. The study includes subjects who are capable of understanding and complying with protocol requirements, as assessed by the investigator, and who have provided informed consent. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The inclusion of a vulnerable population is noted, and the trial ensures that sexually active participants adhere to effective contraception methods throughout the study duration and for a specified period after the last dose.

The clinical trial is designed to evaluate the **efficacy**, safety, tolerability, pharmacokinetics, and immunogenicity of **vedolizumab** administered intravenously in pediatric subjects with active chronic pouchitis. This is an open-label, single-arm, Phase 3 study. The primary objective is to assess the proportion of subjects achieving clinical remission at Week 14, defined by a modified Pouchitis Disease Activity Index (mPDAI) score of less than 5 and a reduction of at least 2 points from baseline. Secondary endpoints include clinical remission and response at Weeks 14 and 34, as well as changes in mPDAI and PDAI scores.

The trial will commence with a screening visit to determine eligibility based on inclusion criteria, such as age between 2 to 17 years, a history of proctocolectomy and ileal pouch-anal anastomosis (IPAA) completed at least one year prior, and active chronic pouchitis with specific mPDAI scores. Following the screening, eligible participants will receive vedolizumab intravenously, with the treatment period lasting up to 30 days. The study includes follow-up visits at Weeks 14 and 34 to assess primary and secondary endpoints, with the end-of-study visit marking the conclusion of participant involvement.

The expected duration of participant involvement is approximately 34 weeks, including the screening, treatment, and follow-up periods. Conditions that may lead to early termination from the study include non-compliance with protocol requirements, adverse events, or withdrawal of consent. The trial is estimated to start recruitment in July 2024 and conclude by June 2029. Participants will be monitored closely throughout the study to ensure safety and adherence to the protocol.

The clinical trial involves the administration of **Vedolizumab**, marketed as Entyvio, which is a **protein**-based medication used in the treatment of pediatric subjects with active chronic pouchitis. Vedolizumab is provided as a 300 mg powder for concentrate for solution for infusion. The pharmaceutical form is a solution for infusion, and it is administered via **intravenous use**. The maximum daily dose is 300 mg, with a total maximum dose of 1800 mg over a treatment period of up to 30 days. Compliance with the dosing schedule is monitored throughout the trial.

In addition to the experimental treatment, several **antibiotics** are used as auxiliary treatments in the study. **Metronidazole** is administered orally in a pharmaceutical form denoted as PHF675. The maximum daily dose is 1500 mg, with a total maximum dose of 9999 mg over a 14-day period. **Amoxicillin Sodium** combined with **Clavulanic Acid** is also administered orally, with a maximum daily dose of 1000 mg and a total maximum dose of 9999 mg over 14 days. The pharmaceutical form is PHF00231MIG.

**Ciprofloxacin Hydrochloride** and **Ciprofloxacin** are administered orally in the form PHF00134MIG, with a maximum daily dose of 1000 mg and a total maximum dose of 9999 mg over 14 days. **Rifamycin Sodium**, marketed as Rifaximin, is administered orally in the form PHF00009MIG, with a maximum daily dose of 1200 mg and a total maximum dose of 9999 mg over 14 days. Lastly, **Vancomycin** is administered orally in the form PHF00230MIG, with a maximum daily dose of 500 mg and a total maximum dose of 9999 mg over 14 days.

All auxiliary antibiotics are administered orally and are not pediatric formulations. The trial ensures that all medications are administered according to the specified dosing schedules, and participant compliance is closely monitored to ensure adherence to the treatment protocols.

The efficacy of **vedolizumab** intravenous in the treatment of pediatric subjects with active chronic pouchitis will be assessed through a series of predefined endpoints. The primary efficacy endpoint is the achievement of clinical remission, defined as a modified Pouchitis Disease Activity Index (mPDAI) score of less than 5 and a reduction of the overall mPDAI score by at least 2 points from baseline, evaluated at Week 14. Secondary endpoints include clinical remission at Week 34, defined similarly to the primary endpoint, and Pouchitis Disease Activity Index (PDAI) remission, defined as a PDAI score of less than 7 and a decrease in the PDAI score by at least 3 points from baseline, assessed at both Week 14 and Week 34.

Additional secondary endpoints involve the assessment of clinical response, defined as a decrease in the mPDAI score by at least 2 points from baseline, at Weeks 14 and 34. Changes from baseline in total mPDAI and PDAI scores, as well as in PDAI clinical symptom, endoscopic, and histologic subscores, will also be evaluated at these timepoints. Furthermore, the study will measure total scores and changes from baseline in the EQ-5D-Y Proxy Version 1.1 at Weeks 14 and 34. These efficacy parameters will be collected and analyzed using validated scales and methods appropriate for the pediatric population involved in the trial.