E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
MS is a chronic autoimmune, inflammatory neurological disease of 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 | 10048393 |
E.1.2 | Term | Multiple sclerosis relapse |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039720 |
E.1.2 | Term | Sclerosis multiple |
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 effectiveness of ocrelizumab therapy in MS patients who were previously enrolled in a Roche sponsored phase IIIb/IV-trial |
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E.2.2 | Secondary objectives of the trial |
• Different effectiveness measures evaluated for ocrelizumab in MS patients who were previously enrolled in a Roche sponsored phase IIIb/IV-trial • To evaluate the safety and tolerability of ocrelizumab therapy in MS patients who were previously enrolled in a Roche sponsored phase IIIb/IV-trial
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Able to comply with the study protocol, in the investigator’s judgment - Completed the treatment period of Roche sponsored ocrelizumab Parent-trial (exception for female patients who were pregnant during CASTING / MA30005 study and are still in the safety follow up period) and who in the opinion of the investigator may benefit from treatment with ocrelizumab - Meet re-treatment criteria with ocrelizumab - For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 6 months after the last dose of study drug |
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E.4 | Principal exclusion criteria |
- Hypersensitivity to ocrelizumab or to any of its excipients - Patients in a severely immunocompromised state until the condition resolves - Evidence of any adverse event potentially attributable to ocrelizumab, for which the local label recommends permanent discontinuation - Existence of a contra-indication as per SmPC - Patients who discontinued ocrelizumab, exemption made for treatment discontinuation because of pregnancy and breastfeeding and continued clinical study assessments |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Evaluate clinical measures related to disease progression over two years in MS patients |
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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) |
1. Time to onset of Confirmed disability progression (CDP) sustained for at least 24 weeks and for at least 48 weeks 2. Proportion of patients who have confirmed disability improvement (CDI), CDP for at least 24 weeks and for at least 48 weeks yearly and over the duration of the Extension study 3. Proportion of patients who have improved, stable or worsened disability compared with baseline (inclusion in Extension study) measured by expanded disability status scale (EDSS)’ 4. Mean change from inclusion in Extension study in EDSS score over the course of the study 5. Time to 20% increase in timed 25-foot walk test (T25FWT); time to 20% increase in timed nine-hole peg test (9HPT) sustained for at least 24 weeks and for at least 48 weeks, and proportion of patients achieving a sustained increase assessed yearly and at the end of the Extension study 6. Time to first protocol-defined event of disease activity 7. Time to first relapse 8. Annualised relapse rate 9. Proportion of patient relapse free, yearly and over the course of the study 10. Proportion of patients with no evidence of protocol-defined disease activity (NEDA) yearly and over the course of the study 11. Proportion of patients with no evidence of progression, measured by EDSS, 9HPT and T25FW (if assessments are available) 12. Proportion of patients with no evidence of progression sustained for at least 24 weeks and no active disease (if assessments are available) 13. Change from baseline in cognitive performance as measured by the Symbol digit modalities test (SDMT) 14. Total number of T1 Gd-enhancing lesions as detected by brain MRI over time 15. Total number of new and/or enlarging T2 lesion as detected by brain MRI over time 16. Change in total T1 hypointense lesion volume over time 17. Total number of fluid-attenuated inversion-recovery (FLAIR) late enhancing lesions as detected by brain MRI over time 18. Change in brain volume (including white and grey matter fractions) as detected by brain MRI over time 19. Time to treatment discontinuation/switch 20. Employment status (Work Productivity and Activity Impairment Questionnaire [WPAI]) 21. SymptoMScreen score 22. Quality of life (Multiple Sclerosis Impact Scale [MSIS]-29) 23. Evaluation of cognition as measured by SDMT assessment 24. Rate and nature of adverse events 25. Changes in vital signs, neurological examinations, clinical laboratory results, locally reviewed MRI for safety (non-MS CNS pathology) and concomitant medications |
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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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 200 |
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 | No |
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 |
Czech Republic |
Denmark |
Estonia |
Finland |
France |
Ireland |
Italy |
Netherlands |
Norway |
Spain |
Sweden |
Turkey |
United Kingdom |
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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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The end of the study is defined as the last patient last visit (LPLV) in the B-cell monitoring of the Follow-Up period i.e. until B-cell repletion and no longer than 2 years (If the patients are receiving other B-cell targeted therapies, then the Follow-up Period is only 48 weeks from the start of other B-cell targeted therapies). |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |