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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E.1.1.1 | Medical condition in easily understood language |
Primary Progressive Multiple Sclerosis (PPMS) |
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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 | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063401 |
E.1.2 | Term | Primary progressive 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 investigate the efficacy of ocrelizumab compared with placebo in patients with primary progressive multiple sclerosis, as measured by the time to sustained disability progression over the treatment period, defined as an increase in EDSS that is sustained for at least 12 weeks. |
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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 sustained disability progression over the treatment period, defined as an increase in EDSS that is
sustained for at least 24 weeks
• Change in 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 wiht PPMS as compared to placebo |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Consenting patients from selected sites who enrolled in the main study WA25056 and who are eligible will be offered the opportunity to participate in optional substudies. 1) Optical Coherence Tomography Exploratory Substudy This Roche sponsored substudy will be conducted at certain selected centers and will be used to evaluate the neuroprotective effect of ocrelizumab as measured by retinal nerve fiber layer (RNFL) thickness and macular volume in both eyes. 2) Multimodal Evoked Potentials This is an Investigator-sponsored substudy entitled “Assessment of ocrelizumab treatment effects on disability of MS patients enrolled in the phase III Orchestra programme using multimodal Evoked Potentials (mEP) and high-resolution electroencephalogram (EEG)”. |
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E.3 | Principal inclusion criteria |
- Adult patients, 18-50 years of age
- Primary Progressive Multiple Sclerosis (according to revised McDonald criteria)
- Expanded Disability Status Scale (EDSS) 3.0 to 6.5 points
- Disease duration from onset of MS symptoms < 15 years if EDSS > 5.0, < 10 years if EDSS ≤ 5.0
- Sexually active male and female patients of reproductive potential must use two methods of contraception throughout the study treatment phase and for 48 weeks for females and 24 weeks for males after the last dose |
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E.4 | Principal exclusion criteria |
- History of relapsing remitting multiple sclerosis, secondary progressive, or progressive relapsing multiple sclerosis at screening
- Contraindications for Magnetic Resonance Imaging (MRI)
- Known presence of other neurologic disorders
- Known active infection or history of or 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 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 lymphocyte trafficking blockers, with alemtuzumab, anti-CD4, cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to onset of 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 | 2 |
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 end of the study has been defined as the date at which the last data point from the last patient, that was required for statistical analysis as defined in the Data Analysis Plan (DAP) was received or, if the study meets its primary end points, when the last data point for generation of follow up analysis generally required by regulatory agency (e.g., 120 days safety update) was 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 | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
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 |