This is an Extension Study of the Roche P-trials to Investigate Safety and Effectiveness of Ocrelizumab in Participants With Multiple Sclerosis (MS)

Study Overview
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Brief Summary
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This extension study will evaluate the effectiveness and safety of ocrelizumab in multiple sclerosis (MS) participants who were previously enrolled in a F. Hoffmann-La Roche (Roche) sponsored ocrelizumab phase IIIb/IV trial (i.e. the Parent, P-trial).

Detailed Description
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This is a single arm, open label, multicenter extension study in participants who completed treatment period with ocrelizumab in the Roche P-trials. Participants will receive treatment with ocrelizumab as single 600 mg infusions every 24 weeks for two years.

Official Title
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A Single Arm, Open Label Multicentre Extension Study To Evaluate The Effectiveness And Safety Of Ocrelizumab In Patients With Multiple Sclerosis Previously Enrolled In A F. Hoffmann-La Roche Sponsored Ocrelizumab Phase IIIb/IV Clinical Trials

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Ocrelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form Able to comply with the study protocol, in the investigator's judgment Completed the treatment period of Roche sponsored ocrelizumab P-trials Exclusion Criteria: Hypersensitivity to ocrelizumab or to any of its excipients. Participantss in a severely immunocompromised state until the condition resolves. Evidence of any adverse event potentially attributable to ocrelizumab, for which the local label recommends permanent discontinuation. Existence of a contra-indication as per SmPC Prohibited concomitant medication as specified in protocol Participants intending to become pregnant during the study or within 6 months after the last dose of the study drug in the parent study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ocrelizumab<br>Participants will receive a single 600-mg infusion of Ocrelizumab every 24 weeks up to Week 72 of this study. | Drug: Ocrelizumab<br>* Participants will receive a 600-mg infusion of Ocrelizumab every 24 months for two years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of CDP sustained for at least 24 weeks and for at least 48 weeks |  | Up to 2 Years | 
| Percentage of participants who have confirmed disability improvement (CDI), CDP for at least 24 weeks and for at least 48 weeks yearly and over the duration of the treatment |  | Up to 2 years | 
| Percentage of participants who have improved, stable or worsened disability compared with baseline | Improved, stable or worsened disability is measured by expanded disability status scale (EDSS) (annually/by epoch and over duration of the study) Stable EDSS is defined as EDSS change +/- 0.5. Worsening is > 0.5 increase of EDSS, Improvement is >0.5 decrease of EDSS | Up to 2 years | 
| Mean change from inclusion in parent study in EDSS score over the course of the treatment |  | Up to 2 years | 
| Time to 20% increase in timed 25-foot walk test (T25FWT) | Time to 20% increase in timed nine-hole peg test (9HPT) sustained for at least 24 weeks and for at least 48 weeks, and proportion of patients achieving a sustained increase assessed yearly and at the end treatment | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first protocol-defined event of disease activity |  | Up to 2 Years | 
| Time to first relapse |  | Up to 2 Years | 
| Annualized relapse rate |  | Up to 2 Years | 
| Percentage of participants relapse free, yearly and over the course of the treatment |  | Up to 2 Years | 
| Percentage of participants with no evidence of protocol-defined disease activity (NEDA) yearly and over the duration of the treatment | Disease activity is defined as at least one the following events: protocol-defined relapse; 24 weeks CDP based on increases in EDSS; a T1 Gadolinium (Gd)-enhanced lesion; or a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI). | Up to 2 Years | 
| Percentage of participants with no evidence of progression (NEP) | NEP is defined as no progression sustained for at least 24 weeks on all of the following three components (CDP; 20% increase in timed T25FWT; 20% increase in timed 9HPT yearly and over the course of the treatment | Up to 2 Years | 
| Percentage of participants with no evidence of progression sustained for at least 24 weeks and no active disease (NEPAD) | NEPAD is defined as no progression on all of the three components of NEP (CDP, T25FWT, 9HPT), no new relapse and no enlarging or new T2 or T1 Gd-enhancing lesion yearly and over the course of the treatment | Up to 2 Years | 
| Change from baseline in cognitive performance as measured by the Symbol digit modalities test (SDMT) |  | Up to 2 Years | 
| Total number of T1 Gd-enhancing lesions as detected by brain MRI over time |  | Up to 2 Years | 
| Total number of new and/or enlarging T2 lesion as detected by brain MRI over time |  | Up to 2 Years | 
| Change in total T1 hypointense lesion volume over time |  | Up to 2 Years | 
| Total number of fluid-attenuated inversion-recovery (FLAIR) late enhancing lesions as detected by brain MRI over time |  | Up to 2 Years | 
| Change in brain volume (grey and white matter) as detected by brain MRI over time |  | Up to 2 Years | 
| Presence and evolution of leptomeningeal follicles as detected by MRI |  | Up to 2 Years | 
| Time to treatment discontinuation/switch |  | Up to 2 Years | 
| Participant reported outcomes: Employment status (Work Productivity and Activity Impairment Questionnaire [WPAI]) |  | Up to 2 Years | 
| Participant reported outcomes: SymptoMScreen Score |  | Up to 2 Years | 
| Participant reported outcomes: Quality of life (QoL) (Multiple Sclerosis Impact Scale [MSIS]-29) |  | Up to 2 Years | 
| Percentage of Participants with Adverse Events |  | Up to 2 Years | 
| Total number of FLAIR late enhancing lesions as detected by brain MRI at the end of the treatment period |  | Up to 2 years |