Long-term Safety and Efficacy Evaluation of Ocrelizumab in Multiple Sclerosis Patients from Phase III Studies

The primary objective of this study is to evaluate the longer-term **safety** of ocrelizumab in participants diagnosed with **Multiple Sclerosis (MS)** who were previously enrolled in Roche-sponsored Phase III pivotal studies. This is clinically relevant as it aims to ensure the continued safety of ocrelizumab, a therapeutic agent used in the management of MS, over an extended period, thereby providing critical data on its risk profile for long-term use.

Secondary objectives include:

• To evaluate the longer-term efficacy of ocrelizumab in the same cohort of participants. This objective is significant as it seeks to confirm the sustained therapeutic benefits of ocrelizumab, ensuring that its efficacy is maintained over time, which is crucial for the long-term management of MS.

The clinical trial involves a total of **1110 participants** diagnosed with **Multiple Sclerosis (MS)**. The study population includes both male and female subjects, with an age range of 18 to 65 years. Participants were selected based on their prior eligibility and participation in one of the Roche-sponsored Parent Studies WA21092, WA21093, or WA25046. These individuals either received ocrelizumab as an investigational medicinal product or were in safety follow-up after treatment discontinuation. The trial population includes a vulnerable group, indicating that special considerations are in place for their protection. Female participants of childbearing potential are required to agree to remain abstinent or use adequate contraception during the treatment period and for a specified duration after the final dose of ocrelizumab. The study does not specify particular lifestyle considerations such as diet or physical activity. The primary objective is to evaluate the longer-term safety of ocrelizumab in this specific cohort.

The clinical trial is designed as a **single-arm**, open-label, extension study to evaluate the long-term safety and efficacy of **ocrelizumab** in patients with **Multiple Sclerosis (MS)**. Participants eligible for this study must have previously been enrolled in one of the Roche-sponsored Phase III pivotal studies, specifically WA21092, WA21093, or WA25046. The primary objective is to assess the incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Secondary endpoints include changes in the Expanded Disability Status Scale (EDSS) score, 9-Hole Peg Test (9HPT), Timed 25-Foot Walk Test (T25FWT), and the number and volume of T1 and T2 lesions over time.

The trial is expected to run until December 31, 2025, with participant recruitment having commenced on May 10, 2022. The study involves multiple visits, starting with an inclusion (screening) visit to confirm eligibility based on prior participation in the specified parent studies and other criteria. Follow-up visits will be scheduled to monitor the safety and efficacy of the treatment, with assessments conducted at regular intervals. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any final evaluations are completed.

Participants are expected to be involved in the study for a maximum treatment period of 417 days. Conditions that may lead to early termination from the study include the occurrence of severe adverse events, withdrawal of consent, or any other medical reasons deemed significant by the investigator. The study drug, Ocrevus 300 mg concentrate for solution for infusion, will be administered via **intravenous infusion**. Female participants of childbearing potential are required to use adequate contraception during the treatment period and for at least six months after the final dose of ocrelizumab, in accordance with the local label requirements.

The clinical trial involves the administration of **Ocrevus**, a pharmaceutical product containing the active substance **ocrelizumab**. Ocrevus is formulated as a **concentrate for solution for infusion** and is intended for intravenous infusion. The product is manufactured by Roche Registration GmbH and is authorized under the marketing authorization number EU/1/17/1231/001. The concentrate is provided in a dosage of 300 mg per vial, with a maximum daily dose of 600 mg. The total maximum dose over the treatment period is 10.20 grams. The treatment period extends up to 417 days. The product has been re-labeled and re-packaged specifically for clinical use in this trial.

Ocrevus is administered via **intravenous infusion**, a route that ensures the direct delivery of the medication into the bloodstream, allowing for precise control over the dosage and timing of administration. The infusion schedule and dosing are designed to maintain therapeutic levels of the drug while minimizing potential side effects. Participant compliance with the dosing regimen is monitored throughout the study to ensure adherence to the protocol and to evaluate the long-term safety and efficacy of ocrelizumab in patients with **multiple sclerosis**.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this single-arm, open-label extension study. The primary objective is to assess the long-term safety of ocrelizumab in participants who have previously been enrolled in Roche-sponsored Phase III pivotal studies. The study does not include a pediatric formulation, and the product is not classified as an orphan drug. The trial is conducted in accordance with regulatory standards to ensure the safety and well-being of all participants.

Efficacy in this clinical trial will be assessed through several secondary endpoints designed to evaluate the impact of **ocrelizumab** on patients with Multiple Sclerosis. The parameters for efficacy evaluation include changes in the Expanded Disability Status Scale (EDSS) score over time, which measures disability progression. Additionally, changes in the 9-Hole Peg Test (9HPT) and Timed 25-Foot Walk Test (T25FWT) will be monitored to assess motor function and mobility. Imaging endpoints will include the number of new, hypointense T1 lesions and the number of new or enlarging T2 lesions, as well as changes in the total volume of T2 lesions and total T1 lesion volume. These assessments will provide a comprehensive evaluation of the drug's efficacy in altering disease progression and neurological function in patients.