Long-Term Safety Evaluation of Filgotinib in Patients with Ulcerative Colitis: An Extension Study

The primary objective of this study is to observe the long-term **safety** of **filgotinib** in subjects with **Ulcerative Colitis** (UC) who have completed or met protocol-specified efficacy discontinuation criteria in a prior filgotinib treatment study. This is clinically relevant as it aims to ensure the sustained safety profile of filgotinib, a Janus kinase inhibitor, which is crucial for its continued use in managing UC, a chronic inflammatory bowel disease.

Secondary objectives include evaluating the effect of filgotinib on the partial Mayo Clinic Score (MCS). This assessment is important as it provides insights into the drug's impact on disease activity and symptom control, which are critical for improving patient outcomes in UC management.

The clinical trial involves a total of **620 participants** diagnosed with **Ulcerative Colitis (UC)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on their prior involvement in a Gilead-sponsored UC parent protocol or any other Gilead/Galapagos-sponsored filgotinib treatment study for UC. The trial does not include a vulnerable population. Participants are required to have completed all necessary procedures or met specific efficacy discontinuation criteria in a previous filgotinib study. Lifestyle considerations include the requirement for female subjects of childbearing potential to undergo regular pregnancy testing and adhere to specified contraceptive methods. Additionally, participants must refrain from receiving live or attenuated vaccines during the study and for 12 weeks following the last dose of the study drug.

The clinical trial is designed to evaluate the long-term safety of **filgotinib** in subjects with **ulcerative colitis** who have previously participated in a Gilead-sponsored filgotinib treatment study. This trial is a randomized, double-blind, controlled study, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thereby minimizing bias. The trial is expected to run until December 2026, with participant recruitment having commenced in January 2017. The study involves several key visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as prior enrollment in a related study and completion of required procedures. Follow-up visits are scheduled to monitor safety through adverse events, clinical laboratory tests, and vital signs, as well as to evaluate the effect of filgotinib on the partial Mayo Clinic Score. The end-of-study visit will conclude the participant's involvement, which is anticipated to last up to 336 days, depending on individual response and adherence to the protocol.

Participants are required to refrain from live or attenuated vaccines during the study and for 12 weeks after the last dose of the study drug. Female participants of childbearing potential must have a negative pregnancy test at Day 1 and agree to monthly pregnancy testing and the use of specified contraception methods throughout the study. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or any adverse events that compromise participant safety. The trial's primary endpoint is the safety of filgotinib, while the secondary endpoint focuses on its effect on the partial Mayo Clinic Score. The study is not classified as low intervention and is categorized as a Phase 3 therapeutic confirmatory trial, emphasizing its focus on safety in an adult population.

The clinical trial involves the administration of **Jyseleca 200 mg film-coated tablets**, which contain the active substance **filgotinib**. These tablets are designed for **oral use** and are administered once daily. The maximum daily dose is 200 mg, with a total maximum dose of 470,400 mg over a treatment period of 336 days. The pharmaceutical form is a film-coated tablet, and the product is authorized under the marketing authorization number EU/1/20/1480/003. The manufacturer of this product is GALAPAGOS, and it is classified under the ATC code L04AA45. Participant compliance with the dosing schedule is monitored throughout the study.

Additionally, the trial includes the use of **Jyseleca 100 mg film-coated tablets**, also containing **filgotinib** as the active substance. These tablets are similarly administered orally once daily, with a maximum daily dose of 100 mg and a total maximum dose of 235,200 mg over the same treatment period of 336 days. The pharmaceutical form remains consistent as a film-coated tablet, and this product is authorized under the marketing authorization number EU/1/20/1480/001. The manufacturer is also GALAPAGOS, and it shares the same ATC classification as the 200 mg formulation. Compliance with the dosing regimen is similarly monitored for participants receiving this dosage.

The trial also includes a **placebo** treatment, which is compositionally identical to the investigational medicinal product (IMP) apart from the active substance. The placebo is administered in the same pharmaceutical form and route as the active treatments, ensuring blinding and maintaining the integrity of the study design. Participant adherence to the placebo regimen is monitored to ensure accurate assessment of the investigational product's efficacy and safety.

The efficacy of the clinical trial evaluating the long-term safety of **filgotinib** in subjects with **Ulcerative Colitis** will be assessed using specific endpoints. The primary endpoint focuses on safety, which will be evaluated through adverse events (AEs), clinical laboratory tests, and vital signs. The secondary endpoint aims to evaluate the effect of filgotinib on the partial Mayo Clinic Score (MCS), a recognized tool for assessing disease activity in Ulcerative Colitis.

Data collection for these endpoints will involve the use of validated scales and laboratory tests. The schedule for measuring and collecting these efficacy parameters will be aligned with the trial's protocol, ensuring systematic and consistent data acquisition throughout the study duration. The analysis of these parameters will be conducted to determine the impact of filgotinib on the specified endpoints, providing insights into its efficacy in managing Ulcerative Colitis over the long term.