ACTIVE RELAPSING MULTIPLE SCLEROSIS (Active RMS) MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification code 10063400 Term: Secondary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous
Conditions
Interventions
Trade Name: Ocrevus 300 mg, solution à diluer pour perfusion
Product Name: Ocrelizumab
Product Code: RO4964913
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ocrelizum
Sponsors
ROCHE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: o Signed informed consent form o Age =18 years at screening o Patients with relapsing forms of multiple sclerosis (RMS) with active disease defined by clinical or imaging features: - At least one clinical relapse over a 6-month period prior to screening - AND/OR at least one T1 gadolinium-enhancing lesion or new and/or enlarging T2 lesion as detected by brain MRI performed over a 3 months period prior to screening with no change of DMT compared to a previous MRI performed within 24 months before screening o 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. o Patients should be beneficiary of healthcare coverage under the social security system Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 570 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: o Diagnosis of primary progressive MS o Inability to complete an MRI o Gadolinium intolerance o Known presence of other neurological disorders, o Patients not able to comply with the study protocol, in the investigator’s judgment o Vulnerable patients o Pregnancy or lactation o Current active infection o Severely immunocompromised state o Known active malignancies o Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study o Lack of peripheral venous access o Significant or uncontrolled somatic disease or any other significant disease that may preclude patient from participating in the study o History or known presence of progressive multifocal leukoencephalopathy o Hypersensitivity to ocrelizumab or to any of the excipients o Receipt of any vaccine within 6 weeks prior to the baseline visit. o Treatment with any investigational agent within 24 weeks of screening or five half-lives of the investigational drug (whichever is longer) or treatment with any experimental procedures for MS within 24 weeks prior to screening o Previous treatment with CD20 B-cell targeted therapies (i.e., rituximab, ocrelizumab, or ofatumumab) in the last 12 months o Any previous treatment with alemtuzumab Campath®/Mabcampath®/Lemtrada®), total body irradiation, or bone marrow transplantation o Previous treatment with natalizumab or fingolimod in the last 8 weeks o Previous treatment with daclizumab in the last 12 weeks o Previous treatment with natalizumab where PML has not been excluded according to specific algorithm in Appendix 5 o Previous treatment with azathioprine, cyclophosphamide, mycophenolate mofetil or methotrexate in the last 12 weeks o Previous treatment with mitoxantrone, cyclosporine or cladribine in the last 2 years o Treatment with dimethyl fumarate within five half-lives of dimethyl fumarate prior to screening o Treatment with biotin within five half-lives of biotin prior to screening o Patients previously treated with teriflunomide, unless an accelerated elimination procedure is implemented before screening visit o Contraindications to or intolerance of antihistamine drugs, oral or IV corticosteroids, including methylprednisolone administered IV, according to the country label, including psychosis not yet controlled by a treatment and hypersensitivity to any of the constituents o Treatment with IV Ig within 12 weeks prior to baseline o Systemic corticosteroid therapy within 4 weeks prior to screening o Treatment with fampridine/dalfampridine (Fampyra®)/Ampyra®) or other symptomatic MS treatment unless on stable dose for =30 days prior to screening. Wherever possible, patients should remain on stable doses throughout the treatment period o Positive serum ? human chorionic gonadotropin (hCG) measured at screening o Positive hepatitis B surface antigen [HBsAg] at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the impact of ocrelizumab on disease activity at W48 in patients with active RMS ;Secondary Objective: • To describe the efficacy of ocrelizumab in active RMS patients • To describe the impact of ocrelizumab on patient reported outcomes (MS symptom severity, treatment satisfaction, work productivity, health-related quality of life, and fatigue) in active RMS patients • To describe the safety of ocrelizumab in active RMS patients;Primary end point(s): Proportion of patients free of disease activity, defined as follow: • No relapse (as per protocol definition*) from enrollment to W48 • AND no T1 gadolinium-enhancing lesion as detected by brain magnetic resonance imaging (MRI) at W48 • AND no new and/or enlarging T2 lesion as detected by brain MRI at W48 Regarding RRMS and SPMS cohorts, the proportion of patients free of disease activity will be described with 95% CI. ;Timepoint(s) of evaluation of this end point: Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Week 24 and Week 48;Secondary end point(s): • Disease activity: Annualized relapse rate, defined as the total number of clinical relapses divided by the number of patient-years of study treatment exposure • Disability: Percentage of patients with stable, improved, or worsened EDSS from enrollment to W48 ; Percentage of patients with disability progression at W24 (CDP24) confirmed at W48 • Mean Change in EDSS from baseline to W48 • Percentage of relapse-free RMS patients by W24 and W48 • Percentage of patients with no T1 gadolinium-enhancing lesion AND no new and/or enlarging T2 lesion as detected by brain MRI at W48 • Percentage of patients with no T1 gadolinium-enhanced lesions as detected by brain MRI at W48 • Percentage of patients with no new and/or enlarging T2 lesions as detected by brain MRI at W48 • Changes in the scores of MS symptom severity scale (SymptoMScreen), Modified Fatigue Impact Scale (MFIS), EuroQol 5 Dimension Questionnaire (EQ-5D-5L with VAS) for health-related quality of life, Work Productivity and Activity Impairment scale (WPAI:SHP), Multiple Sclerosis International Quality Of Life Questionnaire (MusiQOL), Treatment Satisfaction Questionnaire for Medication (TSQM-14) at W24 and at W48. • Occurrence and severity of adverse events, with severity determined according to the NCI CTCAE (v 4.0) | — |
Countries
France
Contacts
Public ContactOpérations Cliniques/ Direction Med
ROCHE SAS
Outcome results
None listed