E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ACTIVE RELAPSING MULTIPLE SCLEROSIS (Active RMS) |
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E.1.1.1 | Medical condition in easily understood language |
ACTIVE RMS is an autoimmune disease that causes inflammation of the insulating membranes (myelin) that surround nerves within the central nervous system. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | Multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063400 |
E.1.2 | Term | Secondary progressive multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the impact of ocrelizumab on disease activity at W48 in patients with active RMS |
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E.2.2 | Secondary objectives of the trial |
• 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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 50 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit Last Subject (Week 76) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |