Long-Term Safety and Efficacy Evaluation of Oral Ozanimod in Patients with Moderately to Severely Active Crohn's Disease: A Phase 3 Multicenter Study

The primary objective of this Phase 3, multicenter, open-label extension study is to demonstrate the long-term **safety** and explore the long-term efficacy of **ozanimod** for the treatment of subjects with moderately to severely active **Crohn's Disease**. This objective is clinically relevant as it aims to provide insights into the sustained therapeutic benefits and potential risks associated with prolonged use of ozanimod, thereby informing treatment strategies for this chronic inflammatory condition. There are no secondary objectives applicable to this study.

The clinical trial involves a total of **516 participants** diagnosed with **moderately to severely active Crohn's Disease**. The study population includes both male and female subjects, with an age range that corresponds to categories 3 and 4, typically encompassing adults and older adults. Participants were selected based on their previous involvement in related induction and maintenance studies, specifically those who did not achieve clinical response or remission, experienced relapse, or completed certain study phases. The trial includes a vulnerable population, indicating that special considerations are in place for their participation. Lifestyle factors such as diet and physical activity are not specified, but female participants of childbearing potential are required to adhere to strict contraceptive measures throughout the study duration. The selection criteria ensure that participants are capable of complying with study requirements and have provided informed consent. The trial aims to assess the long-term safety and efficacy of ozanimod in this patient population.

The clinical trial is a Phase 3, multicenter, open-label extension study designed to evaluate the long-term safety and explore the long-term efficacy of **ozanimod** in patients with moderately to severely active **Crohn's disease**. The trial employs an open-label design, allowing all participants to receive the investigational product, **ozanimod**, administered orally in the form of hard capsules. The study is expected to span from November 14, 2018, to March 24, 2031, with participant involvement potentially lasting up to 264 weeks, depending on individual response and adherence to the study protocol.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as previous participation in related induction or maintenance studies and the ability to comply with study requirements. Following successful screening, participants will enter the treatment phase, where they will receive **ozanimod** and attend regular follow-up visits to monitor safety, efficacy, and adherence to the treatment regimen. These visits will include assessments of clinical response, clinical remission, and endoscopic improvement, with primary endpoints focusing on changes in the Crohn's Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn's Disease (SES-CD).

The end-of-study visit will mark the conclusion of the participant's involvement, during which final assessments will be conducted to evaluate the long-term impact of the treatment. Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or choose to discontinue participation. The study aims to provide valuable insights into the long-term management of **Crohn's disease** with **ozanimod**, contributing to the understanding of its safety and efficacy in this patient population.

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, with each capsule containing the active substance **ozanimod**. The pharmaceutical form is designed for **oral use**. The maximum daily dose of Ozanimod is 0.92 mg, with a total maximum dose of 1700.16 mg over the course of the treatment period. The treatment period extends up to 264 days. The medication is not formulated for pediatric use and is not classified as an orphan drug. The sponsor product code for Ozanimod is RPC1063, and it is manufactured by Receptos, Inc.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the long-term safety and efficacy of Ozanimod in subjects with moderately to severely active **Crohn's Disease**. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

The efficacy of **Ozanimod** in the treatment of moderately to severely active Crohn's Disease will be assessed through a series of primary endpoints. These endpoints include the proportion of subjects achieving a Crohn's Disease Activity Index (CDAI) score of less than 150, a decrease in the Simple Endoscopic Score for Crohn's Disease (SES-CD) from baseline by at least 50%, and the proportion of subjects with an average daily abdominal pain score of 1 point or less, alongside an average daily stool frequency of 3 points or less, with both measures not worsening from baseline. Additional endpoints involve the proportion of subjects with a CDAI reduction from baseline by at least 100 points or achieving a CDAI score of less than 150, and the absence of ulcers greater than 0.5 cm with no segment having an ulcerated surface of 10% or more.

Further efficacy assessments will include changes from baseline in CDAI, the proportion of subjects with a CDAI score of less than 150 while off corticosteroids, and a Crohn's Disease Endoscopic Index of Severity (CDEIS) decrease from baseline by at least 50%. The study will also evaluate clinical response, clinical remission, and endoscopic improvement as a function of baseline and changes in biomarkers such as C-reactive protein, fecal calprotectin, high-density lipoprotein, IgA, and IL-7. Exploratory measurements of SARS-CoV-2 serology will be conducted every 48 weeks to assess the impact of SARS-CoV-2 serologic status on subjects receiving Ozanimod.