Evaluation of Efficacy and Safety of Oral Ozanimod in Pediatric Patients with Moderately to Severely Active Ulcerative Colitis Unresponsive to Conventional Therapy

The primary objective of this study is to evaluate the **efficacy** of ozanimod in pediatric subjects with moderately to severely active ulcerative colitis (UC), specifically assessing clinical remission using the 3-component Mayo Score at Week 52. This is clinically relevant as achieving remission is a critical goal in the management of UC, aiming to improve patient quality of life and reduce disease-related complications.

Secondary objectives include: - Evaluating the efficacy of ozanimod in achieving clinical remission and response at Week 10 and Week 52, using the 3-component Mayo Score. - Assessing symptomatic remission and the time to achieve it. - Evaluating endoscopic improvement by the Mayo Endoscopy Score. - Determining corticosteroid-free remission. - Evaluating the safety and tolerability of two doses of ozanimod. - Characterizing the pharmacokinetics and pharmacodynamic effects of two doses of ozanimod and its major active metabolites.

The clinical trial involves a total of **66 participants** diagnosed with **moderately to severely active ulcerative colitis**. The study population includes both male and female subjects, with an age range that encompasses pediatric patients. Participants were selected based on their diagnosis of ulcerative colitis prior to the screening visit, with evidence of the condition extending beyond the rectum as determined by baseline endoscopy. Additionally, participants have had an inadequate response, loss of response to, or intolerance to at least one treatment for ulcerative colitis, such as oral aminosalicylates, systemic corticosteroids, immunomodulators, or biologic therapy. The trial includes a vulnerable population, indicating careful consideration of ethical standards in the selection process. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is a **randomized**, **double-blind**, controlled study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of oral **ozanimod** in pediatric subjects with moderately to severely active **ulcerative colitis** who have shown an inadequate response to conventional therapy. The trial is structured as a phase 2/3, multicenter study, with an estimated duration extending until March 2034. Participants will be involved in the study for a period that includes multiple visits, starting with a screening visit to confirm eligibility based on criteria such as a prior diagnosis of ulcerative colitis and evidence of the disease extending beyond the rectum. The trial will include follow-up visits to monitor the participants' response to the treatment and assess primary endpoints, such as achieving clinical and histological remission, as well as secondary endpoints like clinical response and symptomatic improvement.

The sequence of study visits is designed to ensure comprehensive monitoring and data collection. The inclusion visit, or screening, will determine eligibility based on the principal inclusion criteria, which include a diagnosis of moderately to severely active ulcerative colitis and an inadequate response to previous treatments. Follow-up visits will occur at regular intervals to assess the primary and secondary endpoints, including clinical remission and response, as well as safety and tolerability. The end-of-study visit will conclude the participant's involvement, summarizing the outcomes and any adverse events experienced during the trial.

Participants are expected to be involved in the study for a duration that allows for adequate assessment of the treatment's efficacy and safety, with the possibility of early termination if specific criteria are met. Early discontinuation may occur starting at Week 5 if a participant's condition does not improve, as indicated by a Partial Mayo score of 7 or higher, or if the score is 6 and worse than baseline, with no improvement in rectal bleeding and stool frequency. The trial's design ensures that data collected will contribute to understanding the potential benefits and risks of ozanimod in treating pediatric ulcerative colitis.

The clinical trial involves the administration of **Ozanimod**, a chemical compound, as the experimental medication. Ozanimod is provided in the form of a hard capsule, designed for **oral use**. The pharmaceutical product is identified by the sponsor product code RPC1063 and is manufactured by Receptos, Inc. The active substance in the medication is ozanimod, with a European substance number of SUB181335. The maximum daily dose and total dose amounts are set at 9999 mg, with the treatment period also capped at 9999 units of time, although specific dosing schedules are not detailed in the provided data. The trial does not utilize a pediatric formulation, and the medication is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are explicitly mentioned. The focus remains on evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of Ozanimod in pediatric subjects with moderately to severely active **ulcerative colitis** who have shown an inadequate response to conventional therapy. Participant compliance with the dosing regimen will be monitored throughout the trial, although specific compliance measures are not detailed in the available information.

The efficacy of **ozanimod** in the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints include the proportion of subjects achieving clinical remission, defined by a Mayo Endoscopy Subscore (MES) of ≤ 1, a Rectal Bleeding Subscore (RBS) of 0, and a Stool Frequency Subscore (SFS) of ≤ 1 with a decrease of ≥ 1 point from baseline SFS. Additionally, histological remission will be evaluated using the Geboes index score of < 2.0 and the Robarts Histopathology Index (RHI) of ≤ 3, with subscores of 0 for both lamina propria neutrophils and neutrophils in the epithelium. Early discontinuation criteria will also be monitored starting at Week 5 if specific conditions are met at two consecutive visits.

Secondary endpoints will assess the proportion of subjects achieving clinical response, defined as a decrease from baseline in the 3-component Mayo score of at least 2 points and at least 35%, and a decrease in RBS of at least 1 point or an absolute RBS of ≤ 1. Other secondary measures include symptomatic improvement of ulcerative colitis (UC), endoscopic improvement, and corticosteroid-free remission at Week 52. Safety and tolerability will be evaluated by monitoring adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation. Pharmacokinetics will be assessed by measuring the steady-state systemic exposure of ozanimod and its metabolite CC112273, while pharmacodynamics will be evaluated by the absolute and percent change from baseline in absolute lymphocyte count (ALC).