C5041010 (APD334-207) An Open Label, Single Arm Study to Evaluate the Efficacy, Pharmacokinetics, and Safety of Etrasimod in Adolescent Participants with Moderately to Severely Active Ulcerative Colitis

The primary objective of this study is to assess the **efficacy** of etrasimod on clinical remission in adolescents aged 12 to less than 18 years with moderately to severely active **ulcerative colitis** (UC) after 52 weeks of treatment. This is clinically relevant as achieving clinical remission is a critical goal in the management of UC, aiming to improve patient outcomes and quality of life.

The secondary objectives include evaluating the pharmacokinetics (PK) of etrasimod after daily doses for up to 52 weeks in adolescents. Additionally, the study aims to assess the efficacy of etrasimod on various clinical endpoints such as endoscopic changes, symptomatic remission, corticosteroid-free remission, and overall clinical response in adolescents with moderately to severely active UC at timepoints up to 52 weeks of treatment. Furthermore, the safety of etrasimod after daily doses in this patient population will be assessed. These secondary objectives are important for understanding the comprehensive impact of etrasimod on disease management and patient safety over an extended period.

The clinical trial involves a total of **23 participants** diagnosed with **moderately to severely active ulcerative colitis**. The study population comprises adolescents aged 12 to less than 18 years, including both male and female subjects. Participants were selected based on their health status, specifically those with active ulcerative colitis, and are allowed to continue receiving a therapeutic dose of select ulcerative colitis medications. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The population includes a vulnerable group, as it involves adolescents, but no further details on lifestyle or additional criteria are provided by the sponsor.

The clinical trial is designed to evaluate the **efficacy**, pharmacokinetics, and safety of **Etrasimod** in adolescent subjects with moderately to severely active **ulcerative colitis**. This is an open-label, single-arm study, which will involve participants aged 12 to less than 18 years. The primary objective is to assess the efficacy of Etrasimod on clinical remission after 52 weeks of treatment. The trial is expected to run from January 10, 2023, to October 31, 2028, with a total duration of 52 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the principal inclusion criteria, which include having moderately to severely active ulcerative colitis and the allowance of certain UC medications. Following the screening, participants will commence treatment with Etrasimod, administered orally in capsule form, with a maximum daily dose of 2 mg. The study will include follow-up visits at regular intervals to monitor the participants' progress and collect data on primary and secondary endpoints. These endpoints include the proportion of subjects achieving clinical remission and endoscopic improvement at weeks 12 and 52, as well as the incidence and severity of adverse events and laboratory abnormalities.

The end-of-study visit will occur at the conclusion of the 52-week treatment period, where final assessments will be conducted to evaluate the overall outcomes of the trial. Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for the participant's safety. The trial is categorized as a Phase 4 study, focusing on the long-term effects and safety of Etrasimod in the specified population.

The clinical trial involves the administration of **Etrasimod**, a chemical compound developed by Arena Pharmaceuticals, Inc. Etrasimod is provided in the form of a **capsule** and is intended for oral administration. The dosage regimen for this trial specifies a maximum daily dose of 2 mg, with the total dose not exceeding 2 mg per day. The treatment period is set for a maximum of 260 days. The primary objective of the trial is to evaluate the efficacy of Etrasimod in achieving clinical remission in adolescent subjects aged 12 to less than 18 years with moderately to severely active **ulcerative colitis** over a 52-week treatment period.

In addition to the experimental treatment, the study may involve the use of a non-experimental treatment in the form of a film-coated tablet. This non-experimental treatment serves as a comparator or standard-of-care therapy, although specific details regarding its administration and dosage are not provided in the available data. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

The efficacy of Etrasimod in the treatment of moderately to severely active **Ulcerative Colitis** in adolescents will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of subjects achieving clinical remission by the Mayo score (MMS) at Week 52. Secondary endpoints include the proportion of subjects achieving clinical remission by MMS at Week 12, endoscopic improvement at Weeks 12 and 52, and symptomatic remission at Weeks 12 and 52. Additional secondary endpoints involve the proportion of subjects achieving clinical response and remission by the Pediatric Ulcerative Colitis Activity Index (PUCAI) at Weeks 12 and 52, as well as pharmacokinetic parameters such as Etrasimod plasma concentration 4 hours post-dose and steady state trough concentration at selected timepoints.

Data collection will occur at specified intervals, with key timepoints at Weeks 12 and 52. The analysis will include the incidence and severity of adverse events, laboratory abnormalities, and changes from baseline in laboratory values, including hematology, serum chemistry, coagulation, and urinalysis. The study will also monitor the incidence of clinically significant vital sign abnormalities and changes from baseline. These assessments will provide a comprehensive evaluation of the efficacy and safety profile of Etrasimod in the target population over the course of the 52-week treatment period.