A Phase 3, Multicenter, Double Blind, Active-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral Ozanimod Compared to Oral Fingolimod in Children and Adolescents with Relapsing Remitting Multiple Sclerosis

The primary objective of this study is to evaluate the efficacy of **ozanimod** compared to **fingolimod** in the treatment of children and adolescents with **Relapsing Remitting Multiple Sclerosis** (RRMS). This is clinically relevant as it aims to determine the potential of ozanimod as an effective treatment option for this patient population, potentially offering an alternative to existing therapies.

Secondary objectives include:

• Core phase: To determine the efficacy, safety, and tolerability of ozanimod.
• Core phase: To measure the amount of ozanimod and certain substances in the participant’s body.
• Extension phase: To determine the efficacy, effectiveness, safety, and tolerability of ozanimod.
• Extension phase: To measure the amount of ozanimod and certain substances in the participant’s body.

The clinical trial involves a total of **40 participants** diagnosed with **Relapsing Remitting Multiple Sclerosis** (RRMS). The study population includes both male and female subjects, with an age range of 18 to 65 years. Participants were selected based on specific criteria, including a confirmed diagnosis of RRMS, a history of at least one relapse in the previous year or two relapses in the past two years, or evidence of disease progression on MRI within the last six months. The **Expanded Disability Status Scale** (EDSS) score of participants ranges from 0 to 5.5, indicating varying levels of disability. All participants must be able to swallow capsules, as this is a requirement for the administration of the study medication. The trial also includes a vulnerable population, ensuring that ethical considerations are in place to protect these individuals. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria. The trial aims to evaluate the efficacy of ozanimod compared to fingolimod in treating RRMS.

The clinical trial is a **Phase III**, multicenter, double-blind, active-controlled study designed to evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of oral **Ozanimod** compared to oral **Fingolimod** in children and adolescents with **Relapsing Remitting Multiple Sclerosis** (RRMS). The trial employs a randomized design to ensure unbiased results, with participants being randomly assigned to receive either the investigational drug or the comparator. The study is expected to commence recruitment on September 2, 2024, and conclude by July 3, 2036, encompassing both core and extension phases.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of RRMS, a history of MS relapses, and the ability to swallow capsules. The core phase will focus on assessing the rate of MS relapse over a two-year period. Follow-up visits will be conducted to monitor the proportion of participants experiencing worsening or improvement in RRMS, the occurrence of adverse events, and the pharmacokinetics of **Ozanimod**. The end-of-study visit will mark the completion of the trial, with data collection on primary and secondary endpoints.

Participant involvement is anticipated to last throughout the core and extension phases, with conditions for early termination including significant adverse events or non-compliance with study protocols. The trial's methodology ensures rigorous monitoring and data collection to achieve its primary objective of comparing the effectiveness of **Ozanimod** against **Fingolimod** in treating RRMS in the pediatric population.

The clinical trial involves the administration of **Ozanimod Hydrochloride** as the experimental medication. Ozanimod Hydrochloride is provided in two pharmaceutical forms: a hard capsule and a sprinkle capsule. The hard capsule form is identified by the sponsor product code BMS-986374 and is manufactured by Bristol-Myers Squibb International Corporation. The active substance, Ozanimod Hydrochloride, is of chemical origin. The medication is administered orally, with a maximum daily dose and total dose amount set at 9999 mg, although specific dosing schedules are not detailed. The sprinkle capsule form also contains Ozanimod Hydrochloride and is similarly administered orally. Both forms are not pediatric formulations and are used in the trial to evaluate their efficacy and safety in treating **Relapsing Remitting Multiple Sclerosis** (RRMS).

In addition to the experimental treatment, the trial includes a comparator treatment using **Fingolimod**. Fingolimod is provided in a hard capsule form and is also administered orally. The product is over-encapsulated to blind against placebo, ensuring the integrity of the double-blind study design. The maximum daily and total dose amounts for Fingolimod are also set at 9999 mg. Fingolimod serves as an active control in the study, allowing for a comparative analysis of the efficacy and safety of Ozanimod Hydrochloride against an established treatment for RRMS.

Participant compliance with the dosing regimen is monitored throughout the trial, although specific compliance measures are not detailed in the provided data. The trial aims to assess the pharmacokinetics and pharmacodynamics of Ozanimod Hydrochloride compared to Fingolimod, providing valuable insights into their respective roles in managing RRMS in children and adolescents.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the rate of **Multiple Sclerosis (MS)** relapse over a period of two years. This will be measured during the core phase of the study. Secondary endpoints include the proportion of participants experiencing worsening or improvement of **Relapsing Remitting Multiple Sclerosis (RRMS)**, the occurrence of adverse events categorized by type, severity, and their relationship to the study drug, early study discontinuation, and the pharmacokinetics of ozanimod, specifically the measurement of its concentration in the participant's body. These secondary endpoints will be assessed during both the core and extension phases of the trial.