E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary Progressive Multiple Sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 18.0 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to investigate whether treatment with BG00012 compared with placebo slows the accumulation of disability not related to relapses in subjects with SPMS. |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of BG00012 compared with placebo on patient-reported outcomes, brain atrophy, and cognitive function |
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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 |
Pharmacogenetics sub-study.
Subjects who consent to participate will provide a blood sample that will be used for exploratory pharmacogenomic analysis. The deoxyribonucleic acid (DNA) will be used to explore identification of specific genetic polymorphisms associated with MS and study treatment response.
Sample Banking for Future Scientific Research
Subjects who consent to participate will give permission for MRI images and leftover blood samples to be used for future scientific research to characterize potential biomarkers.
Lymphocyte subset analysis and processing PBMC for future exploratory analysis.
Subjects who consent to participate will provide blood samples that will be used for lymphocyte subsets, Ig levels, and future PBMC analysis for further lymphophenotyping and functional analysis, if indicated by flow cytometry test results. |
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E.3 | Principal inclusion criteria |
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations.
- Age 18 to 58 years, inclusive, at the time of informed consent.
- Onset of SPMS at least 1 to 2 years prior to randomization. SPMS is defined as relapsing remitting disease followed by progression of disability independent of or not explained by relapses.
- Have EDSS score of 3.0 to 6.5, inclusive.
- Have an MS Severity Score of 4 or higher.
- Have documented confirmed evidence of disease progression independent of clinical relapses over the 1 year prior to randomization as defined in the Study Reference Guide.
- Subjects must be able to successfully complete the assessments associated with each component of the primary endpoint (EDSS, T25FW, 9HPT) at Screening, where successful completion of the T25FW and 9HPT is defined as follows:
•At Screening, T25FW completed in ≤30 seconds
•At Screening, 9HPT completed with each hand in ≤300 seconds.
- All women of childbearing potential (including female subjects who are post menopausal for less than 1 year) and all men must practice effective contraception throughout the study and be willing and able to continue contraception after their last dose of study treatment (women for 30 days; men for 90 days). |
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E.4 | Principal exclusion criteria |
- Have a diagnosis of RRMS or primary progressive MS as defined by the revised McDonald criteria
- Had a recent clinical relapse (within 3 months) prior to randomization
- Subjects for whom MRI is contraindicated (i.e., have pacemakers or other contraindicated implanted metal devices, are allergic to Gd, or have claustrophobia that cannot be medically managed) or for whom the MRI cannot be performed
- Uncontrolled intercurrent illness including, but not limited to- ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; serious or acute liver, kidney, or bone marrow dysfunction; uncontrolled diabetes; serious or acute psychiatric illness that would limit compliance with study requirements
- History of malignancy (subjects with basal cell carcinoma that has been completely excised prior to study entry remain eligible)
- History of human immunodeficiency virus
- History of or positive test result at Screening for hepatitis C virus antibody or hepatitis B virus (defined as positive for hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb]). Subjects with immunity to hepatitis B from either active vaccination (defined as negative HBsAg, positive hepatitis B surface antibody [HBsAb] and negative HBcAb) or from previous natural infection (defined as negative HBsAg, positive HBsAb immunoglobulin G, and positive HBcAb) are eligible to participate in the study
- History of severe allergic or anaphylactic reactions or known drug hypersensitivity to fumaric acid or fumaric acid esters
- Any of the following abnormal blood tests at Screening that are confirmed on repeat testing 2 weeks later:
• ALT/serum glutamate-pyruvate transaminase (SGPT), or AST/serum glutamic-oxaloacetic transaminase (SGOT), or gamma-glutamyl-transferase (GGT) ≥2 times the ULN
• WBC <3500/mm3
• eosinophils >0.7 x 10³/μL or >0.7 GI/L
• absolute lymphocyte count LLN.
- Any of the following abnormal urine tests at Screening confirmed by a second urinalysis 2 weeks later:
• proteinuria (1+ or greater)
• hematuria, without known etiology
• glycosuria, without known etiology
- Any previous treatment with BG00012 or any fumaric acid ester containing product
- Prior treatment with any of the following:
• cladribine
• alemtuzumab
• total lymphoid irradiation
• any therapeutic monoclonal antibody, with the exception of natalizumab (Tysabri®), daclizumab, and rituximab
- Treatment with any of the following medications or procedures within the 6 months prior to randomization:
• mitoxantrone
• cyclophosphamide
• cyclosporine
• azathioprine
• teriflunomide
• methotrexate
• natalizumab
• daclizumab
• rituximab
• fingolimod
• mycophenolate mofetil
• T-cell or T-cell receptor vaccination
• laquinimod
• cytapheresis
- Treatment with any of the following within the 3 months prior to randomization:
• intravenous (IV) steroids or oral corticosteroids
• IV IG
• plasmapheresis
- Treatment with any of the following within the 4 weeks prior to randomization:
• subcutaneous or oral glatiramer acetate
• interferon-β
- Treatment with fampridine within 30 days prior to randomization, unless a stable dose has been maintained for at least 30 days prior to randomization and will be continued for the course of this study.
- Treatment with another investigational drug or approved therapy for investigational use within the 6 months prior to randomization
- Female subjects who are pregnant or currently breastfeeding, or planning to become pregnant while in the study.
- History of drug or alcohol abuse, in the opinion of the Investigator, within 2 years prior to randomization.
- Current enrollment in any interventional clinical study in which an investigational drug or approved therapy for investigational use is administered within 6 months (or 5 half-lives of the agent, whichever is longer) prior to the Baseline Visit.
- Unwillingness or inability to comply with study requirements, including the presence of any condition (physical, mental, or social) that is likely to affect the subject’s ability to comply with the study protocol.
- Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the subject unsuitable for enrollment in this study.
- Previous participation in the study
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is time to disability progression independent of relapse, where progressors are defined as subjects who meet at least 1 of the following criteria confirmed at a second visit ≥6 months later and at Week 108 (or at the last available study visit for subjects who withdraw from the study early):
- EDSS: increase from Baseline of ≥1 point if Baseline EDSS ≤5.5, or ≥0.5 point if Baseline EDSS ≥6.0
- T25FW: ≥20% increase from Baseline in the time taken for the 25-foot walk
- 9HPT: ≥20% increase from Baseline in the time taken for the 9HPT (increase must be confirmed in the same hand)
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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) |
- Change from Baseline to 2 years on the 12 Item Multiple Sclerosis Walking Scale (MSWS 12)
- Change from Baseline to Week 108 in ABILHAND Questionnaire score
- Percentage change from Baseline to Week 108 in whole brain volume
- Change from Baseline to Week 108 in cognitive function as measured by the SDMT
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every 12 weeks, except for the change in the whole brain volume, which will be evaludated at Week 108 |
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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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 130 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Bulgaria |
Canada |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hungary |
Italy |
Netherlands |
Norway |
Poland |
Russian Federation |
Serbia |
Slovakia |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
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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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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 | 5 |
E.8.9.1 | In the Member State concerned days | 19 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |