Open-Label Extension Study Assessing Long-Term Safety of Etrasimod Arginine in Patients with Moderately to Severely Active Ulcerative Colitis

The primary objective of this study is to assess the **safety** of long-term administration of etrasimod in subjects with moderately to severely active **ulcerative colitis** (UC). This is clinically relevant as it aims to ensure that prolonged use of etrasimod does not result in adverse effects, thereby supporting its potential as a sustainable treatment option for UC patients.

The secondary objective is to evaluate the long-term **efficacy** of etrasimod in the same patient population. This assessment is crucial for determining the therapeutic benefits of etrasimod over an extended period, which can inform treatment strategies and improve patient outcomes in managing UC.

The clinical trial involves a total of **587 participants** diagnosed with **ulcerative colitis**, focusing on the safety of long-term administration of etrasimod in individuals with moderately to severely active conditions. The study population includes both male and female subjects, encompassing a diverse age range, including adolescents, adults, and the elderly. Participants were selected based on their prior enrollment in specific Phase 2 and 3 parent studies, with additional criteria ensuring the inclusion of those whose condition has not improved or has worsened. The trial also considers lifestyle factors such as the use of effective contraception methods for females of childbearing potential and requires compliance with protocol assessments. The study includes a vulnerable population, adhering to local laws and regulations for participants under 18 years of age. The selection process ensures a comprehensive evaluation of the safety profile of the investigational treatment in a real-world setting.

The clinical trial is designed to evaluate the long-term safety of **etrasimod arginine** in subjects with moderately to severely active **ulcerative colitis**. This study is an open-label extension, allowing participants from previous Phase 2 and 3 studies to continue receiving the investigational product. The trial is structured as a non-randomized, open-label study, focusing on safety endpoints over an extended period. The estimated duration of the trial is from March 2020 to June 2029, with a maximum treatment period of 260 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as previous enrollment in qualified parent studies and specific clinical conditions. Following the screening, eligible participants will enter the treatment phase, where they will receive **etrasimod arginine** tablets orally. Regular follow-up visits will be scheduled to monitor safety and efficacy, including assessments of treatment-emergent adverse events, laboratory abnormalities, and vital sign changes. Key follow-up assessments will occur at Weeks 52, 104, 156, 208, and 260, with primary endpoints focusing on the incidence of adverse events and laboratory changes.

The end-of-study visit will mark the conclusion of the participant's involvement, where final safety assessments will be conducted. Participants are expected to remain in the study for the full duration unless specific conditions necessitate early termination, such as significant adverse events or withdrawal of consent. The study's design ensures comprehensive monitoring of long-term safety outcomes, contributing valuable data to the understanding of **etrasimod arginine**'s safety profile in the treatment of **ulcerative colitis**.

The clinical trial involves the administration of **Etrasimod Arginine Blue**, a pharmaceutical product developed by Pfizer Inc. This experimental medication is formulated as a **tablet** and is intended for **oral use**. The active substance in the medication is **etrasimod arginine**, which is of chemical origin. The maximum daily dose of Etrasimod Arginine Blue is 2 mg, with a total maximum dose of 3678 mg over the course of the treatment period. The maximum treatment duration is 260 days. The primary objective of the trial is to assess the safety of long-term administration of etrasimod in subjects with moderately to severely active **ulcerative colitis**.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial is designed as an open-label extension study, which implies that all participants will receive the experimental medication without blinding. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen. The trial does not include a pediatric formulation, and the product is not classified as an orphan drug.

Efficacy in the clinical trial of Etrasimod Arginine for subjects with moderately to severely active **Ulcerative Colitis** will be assessed using several key endpoints. The primary efficacy endpoints include the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), as well as the incidence and severity of laboratory abnormalities and changes from treatment baseline in laboratory values such as hematology, serum chemistry, coagulation, and urinalysis. Additionally, the incidence of vital sign abnormalities and changes from treatment baseline will be evaluated.

Secondary efficacy endpoints focus on clinical outcomes, including the proportion of subjects achieving clinical remission at Weeks 52 and 104, both overall and among those who achieved clinical remission at study entry. The trial will also measure the proportion of subjects achieving clinical response at these timepoints. Changes from baseline in the Total Mayo Score (TMS) at Weeks 52 and 104, as well as changes in the Partial Mayo Score (PMS) at Weeks 52, 104, 156, 208, and 260, will be assessed. Furthermore, the proportion of subjects achieving endoscopic improvement at Weeks 52 and 104 will be evaluated.