Evaluation of Filgotinib Efficacy, Safety, and Pharmacokinetics in Pediatric Patients with Moderate to Severe Ulcerative Colitis

The primary objective of this study is to evaluate the **efficacy** of filgotinib in the induction of remission and maintenance of effect in pediatric subjects with moderately to severely active **ulcerative colitis** (UC). This is clinically relevant as achieving and maintaining remission in UC is crucial for improving patient outcomes and quality of life.

Secondary objectives include:

• Evaluating the safety and tolerability of filgotinib in pediatric subjects with UC.
• Assessing the efficacy of a 58-week course of filgotinib to achieve response and remission in pediatric subjects with UC.
• Evaluating the effect of filgotinib on patient-reported outcomes and health-related quality of life in pediatric subjects with UC.
• Characterizing the pharmacokinetics (PK) of filgotinib in pediatric subjects with UC.
• Evaluating the acceptability of the filgotinib pediatric film-coated tablet formulation and the adult tablet formulation in pediatric subjects with UC.

The clinical trial involves a total of **20 participants** diagnosed with **ulcerative colitis**. The study population comprises both male and female subjects aged between 8 and less than 18 years. Participants are required to have a minimum body weight of 15 kg and a documented diagnosis of ulcerative colitis for at least three months. The trial includes individuals who have experienced an inadequate response, loss of response, intolerance, or have medical contraindications to corticosteroids, immunosuppressants, and/or biologic therapy. This includes those dependent on corticosteroids to manage symptoms and who experience disease exacerbation when attempting to reduce corticosteroid use. The selection process ensures the inclusion of a vulnerable population, with no specific lifestyle considerations such as diet or physical activity mentioned. The trial aims to evaluate the efficacy of filgotinib in inducing remission and maintaining its effect in pediatric subjects with ulcerative colitis.

The clinical trial is designed to evaluate the efficacy, safety, tolerability, and pharmacokinetics of **filgotinib** in pediatric subjects aged 8 to less than 18 years with moderately to severely active **ulcerative colitis**. This is a Phase III, multicenter study with a single-arm induction and maintenance approach. The trial is structured as a randomized, double-blind, controlled study, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias. The trial is expected to commence recruitment on November 1, 2024, and conclude by November 8, 2027, with a maximum treatment period of 58 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, weight, and disease characteristics. The primary inclusion criteria include a minimum body weight of 15 kg, a documented diagnosis of **ulcerative colitis** for at least three months, and specific clinical scores indicating disease severity. Following the screening, eligible participants will enter the induction phase, with follow-up visits scheduled to monitor treatment response and safety. The primary endpoints will be assessed at Week 10 and Week 58, focusing on the proportion of subjects achieving clinical remission based on the modified Mayo Clinical Score (mMCS). Secondary endpoints include the incidence of treatment-emergent adverse events, changes in body mass index, and other clinical and pharmacokinetic measures.

The expected length of participant involvement is up to 62 weeks, including follow-up. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or failure to adhere to the study protocol. The study aims to provide comprehensive data on the therapeutic potential of **filgotinib** in managing pediatric **ulcerative colitis**, contributing valuable insights into its clinical application.

The clinical trial involves the administration of **filgotinib**, an experimental medication, in various pharmaceutical forms. The first form is GLPG0634, a film-coated mini-tablet, which is administered orally. The dosage and frequency of administration are determined based on the study protocol, with a maximum treatment period of 58 days. The active substance, filgotinib, is of chemical origin and is provided by Galapagos. Participant compliance with the dosing schedule is monitored throughout the trial.

Additionally, the study includes the use of Jyseleca 100 mg film-coated tablets, which also contain the active substance filgotinib. These tablets are administered orally, and the treatment duration is consistent with the maximum period of 58 days. The tablets are not formulated specifically for pediatric use, and the administration schedule is designed to ensure optimal efficacy and safety in the study population.

The trial further incorporates Jyseleca 200 mg film-coated tablets, which are similarly administered orally. These tablets contain the same active substance, filgotinib, and are provided by Galapagos. The administration follows a structured dosing schedule, with a focus on maintaining participant adherence and monitoring for any adverse effects. The study does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment.

The efficacy of **filgotinib** in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the proportion of subjects achieving clinical remission based on the modified Mayo Clinical Score (mMCS) at Week 10 and Week 58. Secondary endpoints encompass a range of measures, such as the incidence of treatment-emergent adverse events (TEAEs) and laboratory abnormalities through Week 62, changes from baseline in body mass index (BMI) and height velocity at Week 58, and the proportion of subjects achieving clinical remission defined by the Pediatric Ulcerative Colitis Activity Index (PUCAI) at Week 10 and Week 58.

Additional secondary endpoints include the proportion of subjects achieving endoscopic remission, mMCS response, and 6-month corticosteroid-free mMCS remission at specified timepoints. Changes from baseline in TUMMY-UC and IMPACT-III scores at Week 10 and Week 58 will also be evaluated. Pharmacokinetic parameters of filgotinib and its primary metabolite GS-829845 will be assessed, including maximum observed plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve (AUC) over the dosing interval at steady state. The acceptability of the pediatric and adult tablet formulations will be evaluated using the Pediatric Oral Medicine Acceptability Questionnaire for Patients (POMAQ-P).