Phase 3 Multicenter Randomized Double-Blind Placebo-Controlled Trial of Oral Ozanimod for Maintenance in Moderately to Severely Active Crohn's Disease

The primary objective of this study is to demonstrate the efficacy of **ozanimod** compared to placebo in the maintenance of clinical remission and endoscopic response in patients with moderately to severely active Crohn's disease. This is clinically relevant as maintaining remission and achieving endoscopic response are critical goals in the management of Crohn's disease, potentially reducing the need for surgical interventions and improving patient quality of life.

Secondary objectives include: - Demonstrating the efficacy of ozanimod compared to placebo on the maintenance of clinical response. - Demonstrating the efficacy of ozanimod compared to placebo on the maintenance of endoscopic remission and mucosal healing. - Demonstrating the efficacy of ozanimod, compared to placebo, in achieving corticosteroid-free remission. - Demonstrating the efficacy of ozanimod, compared to placebo, on healthcare resource utilization, subject-reported outcomes, and quality of life. - Demonstrating the safety and tolerability of ozanimod as maintenance therapy.

The clinical trial involves a total of **185 participants** diagnosed with **moderately to severely active Crohn's Disease**. 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 completion of the Week 12 efficacy assessments of the Induction Study, demonstrating clinical response or remission. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and compliance. Participants are required to have the ability to comply with study procedures and provide informed consent. Female participants of childbearing potential must adhere to effective contraceptive methods throughout the study duration. The trial aims to evaluate the efficacy of ozanimod compared to placebo in maintaining clinical remission and endoscopic response.

The clinical trial is a **Phase 3**, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy of **ozanimod** as a maintenance therapy for patients with moderately to severely active **Crohn's disease**. The primary objective is to demonstrate the efficacy of ozanimod compared to placebo in maintaining clinical remission and endoscopic response. The trial is expected to run from June 27, 2018, to March 24, 2026, with a maximum treatment period of 371 days for each participant.

Participants will be randomly assigned to receive either ozanimod or a placebo, both administered in the form of hard-gelatin capsules for oral use. The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress and assess outcomes, and a final end-of-study visit. The inclusion criteria require participants to have completed the Week 12 efficacy assessments of a prior induction study and to be in clinical response or remission. Female participants of childbearing potential must adhere to effective contraception methods throughout the study.

The primary endpoints include the proportion of subjects achieving a Crohn's Disease Activity Index (CDAI) score of less than 150 and a significant decrease in the Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 52. Secondary endpoints focus on various measures of clinical response, including reductions in CDAI scores, improvements in abdominal pain and stool frequency, and histologic improvements. Participants' involvement is expected to last up to 52 weeks, with conditions for early termination including non-compliance with study protocols or adverse events that compromise participant safety.

The clinical trial involves the administration of **Ozanimod**, a chemical compound, as the experimental medication. Ozanimod is provided in the form of hard-gelatin capsules, with each capsule containing the active substance **ozanimod**. The pharmaceutical form is specified as "CAPSULE, HARD," and the medication is intended for **oral use**. The maximum daily dose of Ozanimod is 0.92 mg, with a total maximum dose of 341.32 mg over the treatment period. The maximum treatment period is 371 days. The medication is manufactured by Receptos, Inc., and is identified by the sponsor product code RPC1063. Participant compliance with the dosing schedule will be monitored throughout the study.

The study also includes a **placebo** group, which receives placebo capsules that match the appearance of the Ozanimod capsules. These placebo capsules are also in the form of hard-gelatin capsules and are intended for oral use. The placebo serves as a comparator treatment to evaluate the efficacy of Ozanimod in maintaining clinical remission and endoscopic response in participants with moderately to severely active **Crohn's disease**. The placebo capsules do not contain any active substance and are used to ensure the double-blind nature of the study.

The efficacy of **Ozanimod** as a maintenance therapy for moderately to severely active Crohn's Disease will be assessed in a Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial. The primary endpoints for evaluating efficacy include the proportion of subjects achieving a Crohn's Disease Activity Index (CDAI) score of less than 150 and a Simple Endoscopic Score for Crohn's Disease (SES-CD) decrease from baseline of at least 50% at Week 52. Secondary endpoints will further assess efficacy through various measures, such as the proportion of subjects with a CDAI reduction from baseline of at least 100 points, maintenance of a CDAI score of less than 150 while remaining corticosteroid-free, and histologic improvement based on Global Histologic Disease Activity Score (GHAS) changes at Week 52.

Data collection will occur at specified timepoints, with the primary analysis conducted at Week 52. The efficacy parameters will be measured using validated scales and scores, including the CDAI and SES-CD, to ensure accurate and reliable assessment of clinical remission and endoscopic response. The trial aims to demonstrate the superiority of Ozanimod over placebo in maintaining clinical remission and achieving endoscopic response in subjects with Crohn's Disease. The study will adhere to rigorous standards for data collection and analysis to ensure the validity and reliability of the results.