A Study to Provide Complementary Efficacy, Safety and Patient Reported Outcomes Data in Participants With Active Relapsing Forms of Multiple Sclerosis (MS) in a Pragmatic Setting

Study Overview
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Brief Summary
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This national, open-label study is designed to give complementary efficacy, safety and patient reported outcomes (PROs) data in participants with active relapsing forms of MS. Participants will receive a maximum of 2 treatment cycles of ocrelizumab infusions: an initial dose of two 300 milligram (mg) infusions separated by 14 days followed by one single infusion of 600 mg ocrelizumab 24 weeks after the first infusion. Disease activity is determined by clinical relapses and/or Magnetic Resonance Imaging (MRI) activity.

Official Title
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An Open-Label, Single-Arm Phase IV Study To Assess Ocrelizumab Efficacy, Safety, And Impact On Patient Reported Outcomes (PROS) In Patients With Active Relapsing Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Ocrelizumab 300 mg
* Drug: Ocrelizumab 600 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >/=18 years at screening Patients with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features: (i) at least one clinical relapse over a 6-month period prior to screening; (ii) AND/OR at least one T1 gadolinium-enhancing lesion or new and/or enlarging T2 lesion as detected by brain Magnetic Resonance Imaging (MRI) performed over a 3 months period prior to screening with no change of Disease-Modifying Treatment(s) (DMT) compared to a previous MRI performed within 24 months before screening For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 12 months after the last dose of ocrelizumab Participants should be beneficiary of healthcare coverage under the social security system Exclusion Criteria: Diagnosis of primary progressive MS Inability to complete an MRI (contraindications for MRI include but are not restricted to weight ≥140 kg, pacemaker, cochlear implants, presence of foreign substances in the eye, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, etc…) Gadolinium intolerance History of ischemic cerebrovascular disorders (e.g., stroke, transient ischemic attack) or ischemia of the spinal cord History or known presence of central nervous system (CNS) or spinal cord tumor (e.g., meningioma, glioma) History or known presence of potential metabolic causes of myelopathy (e.g., untreated vitamin B12 deficiency) History or known presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, human T-lymphotropic virus 1 (HTLV-1), herpes zoster myelopathy) History of genetically inherited progressive CNS degenerative disorder (e.g., hereditary paraparesis; MELAS [mitochondrial myopathy, encephalopathy, lactic acidosis, stroke] syndrome) Neuromyelitis optica History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sjogren's syndrome, Behçet's disease, sarcoidosis) History of severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression) Vulnerable patients (Patient referred to in Articles L. 1121-5 to L. 1121-8 and L. 1122-1-2 of the French Public Health Code)

Ages Eligible for Study
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Minimum Age: 18 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 Treatment Cycles<br>Each participant will receive an initial dose of two 300 mg infusions of Ocrelizumab each separated by 14 days followed by one single dose of 600 mg 24 weeks after the initial dose. | Drug: Ocrelizumab 300 mg<br>* Two doses of 300 mg infusion administered 14 days apart.<br>Drug: Ocrelizumab 600 mg<br>* A single does of 600 mg infusion administered 24 weeks after the initial dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants free of disease activity | This outcome measure evaluates the impact of ocrelizumab on disease activity in participants with active Relapsing Multiple Sclerosis (RMS). Freedom of disease activity is defined as participant without any relapse from enrollment to Week 48 and without T1 Gadolinium-enhancing lesion detected by brain MRI at Week 48 and without any new and/or enlarging T2 lesion detected by brain MRI at Week 48. | From Enrollment to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized relapse rate | Annualized relapse rate is defined as the total number of clinical relapses divided by the number of participant-years of study treatment exposure. This outcome measure describes the efficacy of ocrelizumab in active RMS participants. | At Week 48 | 
| Percentage of participants with stable, improved, or worsened expanded disability status scale (EDSS) | This outcome measure describes the efficacy of ocrelizumab in active RMS participants. | From Enrollment to Week 48 | 
| Percentage of participants with confirmed disability progression at Week 24 (CDP24) | This outcome measure describes the efficacy of ocrelizumab in active RMS participants. | At Week 48 | 
| Mean Change in EDSS | This outcome measure describes the efficacy of ocrelizumab in active RMS participants. | From Baseline to Week 48 | 
| Percentage of relapse-free RMS participants | This outcome measure describes the efficacy of ocrelizumab in active RMS participants. | From Enrollment to Week 24 and Week 48 | 
| Percentage of participants with no T1 gadolinium-enhancing lesion and no new and/or enlarging T2 lesion as detected by brain MRI | This outcome measure describes the efficacy of ocrelizumab in active RMS participants. | At Week 48 | 
| Percentage of participants with no T1 gadolinium-enhancing lesion as detected by brain MRI | This outcome measure describes the efficacy of ocrelizumab in active RMS participants. | At Week 48 | 
| Percentage of participants with no new and/or enlarging T2 lesion as detected by brain MRI | This outcome measure evaluates the impact of ocrelizumab on disease activity in participants with active RMS. | At Week 48 | 
| Change in the score of MS symptom severity scale (SymptoMScreen) | This outcome measure describes the impact of ocrelizumab on patient reported outcomes (MS symptom severity, fatigue, health-related quality of life with standard and disease specific scales, work productivity, and treatment satisfaction) in active RMS patients. | At Week 24 and Week 48 | 
| Change in the score of Modified Fatigue Impact Scale (MFIS) | This outcome measure describes the impact of ocrelizumab on patient reported outcomes (MS symptom severity, fatigue, health-related quality of life with standard and disease specific scales, work productivity, and treatment satisfaction) in active RMS patients. | At Week 24 and Week 48 | 
| Change in the score of EuroQol 5-Dimension Questionnaire (EQ-5D-5L with Visual Analogue Scale (VAS)) for health-related quality of life | This outcome measure describes the impact of ocrelizumab on patient reported outcomes (MS symptom severity, fatigue, health-related quality of life with standard and disease specific scales, work productivity, and treatment satisfaction) in active RMS patients. | At Week 24 and Week 48 | 
| Change in the score of Work Productivity and Activity Impairment scale (WPAI:SHP) | This outcome measure describes the impact of ocrelizumab on patient reported outcomes (MS symptom severity, fatigue, health-related quality of life with standard and disease specific scales, work productivity, and treatment satisfaction) in active RMS patients. | At Week 24 and Week 48 | 
| Change in the score of Multiple Sclerosis International Quality Of Life Questionnaire (MusiQOL) | This outcome measure describes the impact of ocrelizumab on patient reported outcomes (MS symptom severity, fatigue, health-related quality of life with standard and disease specific scales, work productivity, and treatment satisfaction) in active RMS patients. | At Week 24 and Week 48 | 
| Change in the score of Treatment Satisfaction Questionnaire for Medication (TSQM-14) | This outcome measure describes the impact of ocrelizumab on patient reported outcomes (MS symptom severity, fatigue, health-related quality of life with standard and disease specific scales, work productivity, and treatment satisfaction) in active RMS patients. | At Week 24 and Week 48 | 
| Percentage of Participants with Adverse Events (AE) | This outcome measure describes ocrelizumab safety in active RMS patients. Severity of AEs is determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.0) | From Baseline to Week 48 |