E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Progressive Multiple Sclerosis (PPMS) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063401 |
E.1.2 | Term | Primary progressive multiple sclerosis |
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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 investigate the efficacy of ocrelizumab compared with placebo in patients with primary progressive multiple sclerosis, as measured by the time to onset of sustained disability progression over the treatment period, defined as an increase in EDSS that is sustained for at least 12 weeks, based on regularly scheduled visits. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of ocrelizumab compared with placebo, as reflected by the following: • Time to onset of sustained disability progression over the treatment period, defined as an increase in EDSS that is sustained for at least 24 weeks, based on regularly scheduled visits • Change in timed 25-foot timed walk from baseline to Week 120 • Change in total volume of T2 lesions on MRI scans of the brain from baseline to week 120 • To evaluate safety and tolerability of ocrelizumab in patients with PPMS as compared to placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Ages 18-50 years inclusive - Diagnosis of Primary Progressive Multiple Sclerosis in accordance with the revised McDonald criteria (2005) - Expanded Disability Status Scale (EDSS) 3.0 to 6.5 points - Disease duration from onset of MS symptoms a. less than 15 years in patients with an EDSS at screening > 5.0 b. less than 10 years in patients with an EDSS at screening ≤ 5.0 - For sexually active male and female patients of reproductive potential, use of reliable means of contraception as described below as a minimum: Two methods of contraception throughout the trial, including the active treatment phase and for 48 weeks after the last dose of ocrelizumab, or until their B-cells have repleted, which is longer. |
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E.4 | Principal exclusion criteria |
- History of relapsing remitting multiple sclerosis, secondary progressive, or progressive relapsing multiple sclerosis at screening - Inability to complete an MRI - Known presence of other neurologic disorders - Known active bacterial, viral, fungal, mycobacterial infection or other infection or any major episode of infection requiring hospitalization or treatment with i.v antibiotics within 4 weeks prior to baseline visit or oral antiobiotics within 2 weeks prior to basline visit. - history or known presence of recurrent or chronic infection - History of cancer, including solid tumors and hematological malignancies (except for basal cell, in situ squamous cell carcinomas of the skin and in situ carcinoma of the cervix of the uterus that have been excised and resolved) - Previous treatment with B-cell targeted therapies (e.g. rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab) - Any previous treatment with alemtuzumab, anti-CD4, cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation - Any previous treatment with lymphocyte trafficking blockers
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to sustained disability progression, defined as an increase in Expanded Disability Status Scale (EDSS) score that is sustained for at least 12 weeks from baseline to sustained disability progression |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 105 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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the date at which the last data point from the last patient is received |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |