Evaluation of Ocrelizumab Efficacy and Safety in Progressive Multiple Sclerosis: A 4-Year Open-Label, Single-Arm Study

The primary objective of this study is to evaluate the **effectiveness** of ocrelizumab treatment in patients with **progressive multiple sclerosis** (PMS). This is clinically relevant as it aims to determine the therapeutic impact of ocrelizumab on the disease course, potentially offering insights into improved management strategies for PMS, a condition characterized by a gradual worsening of neurological function.

Secondary objectives include:

• Evaluating the effectiveness of ocrelizumab treatment in PMS patients using a range of patient-relevant measures and imaging outcomes. This objective seeks to provide a comprehensive assessment of the treatment's impact on patient quality of life and disease progression through various clinical and imaging parameters.
• Evaluating the safety and tolerability of ocrelizumab in PMS patients. This is crucial for understanding the risk-benefit profile of the treatment, ensuring that it is not only effective but also safe for long-term use in this patient population.

The clinical trial involves a total of **360 participants** diagnosed with **progressive multiple sclerosis (PMS)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including a confirmed diagnosis of PMS according to established guidelines, and an **Expanded Disability Status Scale (EDSS)** score of 6.5 or less at screening. The trial population is characterized by individuals who have demonstrated disability progression independent of relapse over the two years prior to screening. Participants are required to have experience using a smartphone and connecting to Wi-Fi networks. The study includes both genders and considers vulnerable populations. Lifestyle factors such as diet and physical activity are not specified, but women of childbearing potential must agree to use acceptable contraceptive methods during the treatment period and for a specified duration after the last dose of the study drug.

The clinical trial is designed to evaluate the effectiveness and safety of **ocrelizumab** treatment in patients with **progressive multiple sclerosis**. This study is an open-label, single-arm trial with an estimated duration of four years, concluding in September 2026. Participants will be administered **Ocrevus 300 mg concentrate for solution for infusion** via intravenous infusion. The trial will assess both primary and secondary endpoints, including the proportion of patients with no evidence of progression sustained for at least 24 weeks and changes in cognitive function and patient-reported outcomes.

The trial will commence with a screening visit to confirm eligibility based on criteria such as a definite diagnosis of progressive multiple sclerosis and an Expanded Disability Status Scale (EDSS) score of ≤6.5. Participants must also demonstrate disability progression independent of relapse over the two years prior to screening. Following the screening, participants will undergo regular follow-up visits to monitor treatment efficacy and safety, with assessments including cognitive tests and MRI volumetric measures. The end-of-study visit will evaluate the overall outcomes and any adverse events experienced during the trial.

Participant involvement is expected to last up to 192 weeks, with conditions for early termination including adverse events or withdrawal of consent. The trial will utilize a comprehensive set of assessments to ensure a thorough evaluation of the treatment's impact on disease progression and patient quality of life. The study's design and methodology aim to provide robust data on the long-term effects of ocrelizumab in managing progressive multiple sclerosis.

The clinical trial involves the administration of **Ocrevus** (ocrelizumab), a **concentrate for solution for infusion**. This experimental medication is provided in a dosage of 300 mg and is administered via **intravenous infusion**. The maximum daily dose is 600 mg, with a total maximum dose of 4.8 g over the treatment period. The treatment period extends up to 192 weeks. Ocrevus is a protein-based therapeutic agent developed by Roche Registration GmbH, and it is not a pediatric formulation.

In addition to the experimental treatment, **Methylprednisolone** is used as a non-experimental treatment. It is provided as a **powder and solvent for solution for injection/infusion** with a dosage of 500 mg. This synthetic glucocorticoid is also administered via **intravenous infusion**. The maximum daily dose is 100 mg, with a total maximum dose of 900 mg over the treatment period of 192 weeks. Methylprednisolone is a chemical-based compound provided by Kent Pharma UK Limited.

**Diphenhydramine Hydrochloride** is included as an auxiliary treatment in the form of **tablets**. Each tablet contains 50 mg of the active substance, and it is classified as a synthetic antihistamine. The maximum daily dose is 5 g, with a total maximum dose of 45 g over the treatment period. This chemical-based compound is manufactured by Crescent Pharma Limited.

**Paracetamol** is also used as an auxiliary treatment, provided as **comprimate efervescente** for oral administration. Each dose contains 1000 mg of paracetamol, a synthetic analgesic and antipyretic compound. The maximum daily dose is 1 g, with a total maximum dose of 9 g over the treatment period. This chemical-based compound is produced by Accord Healthcare Polska Sp. z o.o.

The efficacy of the treatment in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints include the proportion of patients with no evidence of progression (NEP) sustained for at least 24 weeks and the proportion of patients with NEP and no active disease (NEPAD) sustained for at least 24 weeks. Secondary endpoints will evaluate various aspects of patient health and disease progression. These include changes from baseline in cognitive function as measured by the Symbol Digit Modalities Test (SDMT) and the Brief Visuospatial Memory Test – Revised (BVMT-R), as well as changes in patient-reported outcomes such as the Multiple Sclerosis Impact Scale -29 and the Multiple Sclerosis Walking Scale -12 items. Additional secondary endpoints include the mean change from baseline in the Expanded Disability Status Scale (EDSS) score, time to onset of confirmed disability progression, and changes in MRI volumetric measures and lesion parameters.

Data collection will occur at specified intervals throughout the study, with assessments conducted using validated scales and tests. The Symbol Digit Modalities Test and the Brief Visuospatial Memory Test – Revised will be utilized to measure cognitive function changes. Patient-reported outcomes will be gathered using various scales, including the ABILHAND-56 Questionnaire and the Fatigue Scale for Motor and Cognitive function. MRI scans will be used to assess changes in brain volume and lesion characteristics. The efficacy parameters will be analyzed to determine the treatment's impact on disease progression and patient quality of life over the course of the study.