E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-Remitting Multiple Sclerosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting 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 evaluate the long-term safety profile of BG00012
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term efficacy of BG00012 using clinical endpoints (including relapse and annualised relapse rate [ARR]) and disability progression (Expanded Disability Status Scale [EDSS]).
To evaluate further the long-term effects of BG00012 on MS brain lesions on magnetic resonance imaging (MRI) scans in subjects who had MRI scans as part of Studies 109MS301 and 109MS302. The following MRI endpoints will be evaluated in the subset of subjects who participated in the MRI scans: number and volume of new or newly-enlarging T2 lesions, number and volume of T1 hypointense lesions, brain atrophy, and magnetization transfer ratio (MTR).
To evaluate the long-term effects of BG00012 on health economics assessments and the visual function test. The endpoints are the SF-36 and EQ-5D quality of life questionnaire, and visual function test scores.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Must give written informed consent and any authorizations required by local law (e.g. Protected Health Information [PHI]). 2. Aged 18 to 55 years old, inclusive, at the time of informed consent and enrolment into the 109MS301 or 109MS302 trial. 3. Subjects who participated in and completed as per protocol previous BG00012 clinical studies 109MS301 and 109MS302, including those subjects who received an open-label, approved MS therapy and completed a modified visit schedule, are eligible to participate in this study. |
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E.4 | Principal exclusion criteria |
Reasons for study exclusion include:
Any significant change in medical history in subjects from 109MS301 or 109MS302, including laboratory tests, or current clinically significant condition that in the opinion of the Investigator would have excluded the subjects' participation from their previous study. The Investigator must re-review the subject's medical fitness for participation and consider any diseases that would preclude treatment.
Subjects from 109MS301 or 109MS302 who discontinued oral study treatment due to an AE or due to reasons other than protocol-defined relapse/disability progression.
Subjects from 109MS301 or 109MS302 who discontinued study treatment due to disability progression or relapses and did not follow the modified weekly schedule up to Week 96.
Alanine transaminase (ALT), aspartate transaminase (AST), or gamma-glutamyl-transferase (GGT) >3 times the upper limit of normal (ULN).
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Assessments:
Relapse assessment, EDSS, MRI analysis (on subjects who had MRI scans as part of Studies 109MS301 and 109MS302), visual function as measured by low-contrast Sloan letter charts.
Efficacy:
Annualised Relapse Rate [ARR] will be summarised for the two years in the extension study as well as the two years in the previous Phase 3 studies (109MS301 and 109MS302). Also the ARR for a 4-year total for each treatment group (original 240 mg BID BG00012, original 240 mg TID BG00012, placebo/240 mg BID BG00012, placebo/240 mg TID BG00012) will be analysed.
Health Economic Assessments:
SF-36, EQ-5D Quality of Life Questionnaire
Safety Assessments: Physical examination, including vital signs, blood chemistry, haematology, urinanalysis, urine cytology, adverse event monitoring.
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Parallel-group, randomized, dose-blind, dose-comparison extension study |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 160 |
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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Last Patient, Last Visit (LPLV) for final collection of data for the primary outcome. |
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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 | 4 |
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 | 4 |