| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsing Multiple Sclerosis |
|
| E.1.1.1 | Medical condition in easily understood language |
| Relapsing Multiple Sclerosis |
|
| 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 | 16.1 |
| 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 |
|
| 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 this study is to determine the efficacy of BIIB017 in reducing the Annualized Relapse Rate (ARR) in subjects with RMS at 1 year. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to determine, whether
BIIB017, at 1 year when compared with placebo, is effective in:
reducing the total number of new or newly enlarging T2 hyperintense lesions on brain MRI scans reducing the proportion of subjects who relapsed slowing the progression of disability as measured by at least a 1.0 point increase on the Expanded Disability Status Scale (EDSS) from baseline EDSS ≥ 1.0 that is sustained for 12 weeks, or at least a 1.5 point increase on the EDSS from baseline EDSS = 0 that is sustained for 12 weeks.
|
|
| 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 |
Protocol 105MS301, Version 5.1, 27 Mar 2012
This sub-study will examine the progression of BIIB017’s treatment effect by comparing the accumulation of new gadolinium (Gd+) lesions on cranial MRI over a 6-month period in BIIB017 versus placebo-treated subjects. In addition, in a subset of subjects, the potential associations between an effect on MRI and biological markers of Type 1 interferon (IFN) receptor activation will be evaluated. |
|
| E.3 | Principal inclusion criteria |
To be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of randomization, Day 1:
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
2. Aged 18 to 65 years old, inclusive, at the time of informed consent.
3. Must have a confirmed diagnosis of relapsing MS, as defined by McDonald criteria #1-4.
4. Must have an EDSS score between 0.0 and 5.0.
5. Must have experienced at least 2 relapses that have been medically documented within the last 3 years with at least one of these relapses having occurred within the past 12 months prior to randomization (Day 1).
6. All male subjects and female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 3 months, after their last dose of study treatment. |
|
| E.4 | Principal exclusion criteria |
Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of randomization, Day 1: Medical History
1. Primary progressive, secondary progressive, or progressive relapsing MS (as defined by Lublin and Reingold, 1996). These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Subjects with these conditions may also have superimposed relapse, but are distinguished from relapsing subjects by the lack of clinically stable periods or clinical improvement.
2. History of severe allergic or anaphylactic reactions or known hypersensitivity.
3. Prior treatment with interferon cannot exceed 4 weeks and subjects must have discontinued interferon treatment 6 months prior to Baseline.
4. Known allergy to any component of the BIIB017 formulation.
5. History of any clinically significant (as determined by the Investigator) cardiac,endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary,
neurologic, dermatologic, psychiatric, and renal, or other major disease that would preclude participation in a clinical trial.
6. History of malignant disease, including solid tumors and hematologic malignancies
(with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
7. History of seizure disorder or unexplained blackouts OR history of a seizure within 3 months prior to Baseline.
8. History of suicidal ideation within 3 months prior to Baseline or an episode of severe depression within 3 months prior to Baseline. Severe depression is defined as an episode of depression that requires hospitalization, or at the discretion of the Investigator.
9. Clinically significant abnormal electrocardiogram (ECG) values as determined by the Investigator.
10. Known history of Human Immunodeficiency Virus (HIV).
11. Known history or positive test result for hepatitis C antibody (HCV Ab), or current hepatitis B infection at Screening. Subjects with immunity to hepatitis B from either active vaccination or from previous natural infection are eligible to participate in the study
12. Abnormal screening blood tests exceeding any of the limits defined below:
• Alanine transaminase/serum glutamate pyruvate transaminase (ALT/SGPT)
greater than 2 times the upper limit of normal (>2 × ULN) or aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) >2 × ULN or bilirubin >1.5 × ULN.
• Total white blood cell count (WBC) < 3,700 /mm3
• Absolute Neutrophil Count (ANC) of < 1,500 /mm3
• Platelet count <150,000 c/mm3
• Hemoglobin <10 g/dL in female subjects; <11 g/dL in male subjects
• Serum creatinine >ULN
• Prothrombin time (PT) or activated partial thromboplastin time (aPTT) >1.2 × ULN
13. An MS relapse that has occurred within the 50 days prior to randomization and/or the subject has not stabilized from a previous relapse prior to randomization (Day 1).
Treatment history:
14. Any previous treatment with BIIB017.
15. History of hypersensitivity or intolerance to acetaminophen (paracetamol), ibuprofen, naproxen, or aspirin that would preclude use of at least one of these during the study.
16. Treatment with other agents to treat MS symptoms or underlying disease as specified in Table P.43 in protocol.
17. Treatment with another investigational drug or approved therapy for investigational use within the 6 months prior to randomization (Day 1).
Miscellaneous
18. Female subjects considering becoming pregnant while in the study.
19. Female subjects of childbearing potential who have a positive pregnancy test at either the Screening Visit or the Day 1 (Baseline) Visit may not be enrolled into this study.
20. Female subjects who are pregnant or currently breastfeeding.
21. History of drug or alcohol abuse (as defined by the Investigator) within 2 years prior to Day 1.
22. Unable to perform the Timed 25-Foot Walk, Nine-Hole Peg Test (9HPT) with both upper extremities, and PASAT 3.
23. Unable to perform visual function tests.
24. Subjects for whom MRI is contraindicated, i.e., who have pacemakers or other contraindicated implanted metal devices, are allergic to gadolinium, or have claustrophobia that cannot be medically managed.
25. Current enrollment in any other investigational drug study.
26. Previous participation in this study.
27. Elective surgery performed from 2 weeks prior to randomization (Day 1) or scheduled through the end of the study.
28. Unwillingness or inability to comply with the requirements of the protocol including the presence of any condition (physical, mental or social) that is likely to affect the subject’s ability to comply with the protocol.
29. Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the subject unsuitable for enrollment. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of this study is to determine the efficacy of BIIB017 in reducing the Annualized Relapse Rate (ARR) in subjects with relapsing Multiple Sclerosis (MS) at 1 year. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The secondary endpoints of this study are to determine, whether
BIIB017, at 1 year when compared with placebo, is effective in:
reducing the total number of new or newly enlarging T2 hyperintense lesions on brain MRI scans reducing the proportion of subjects who relapsed slowing the progression of disability as measured by at least a 1.0 point increase on the Expanded Disability Status Scale (EDSS) from baseline EDSS ≥ 1.0 that is sustained for 12 weeks, or at least a 1.5 point increase on the EDSS from baseline EDSS = 0 that is sustained for 12 weeks.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | 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 | Yes |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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 | 3 |
| 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 | 18 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 170 |
| 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 |
| Belgium |
| Bulgaria |
| Canada |
| France |
| Greece |
| Croatia |
| Netherlands |
| New Zealand |
| Romania |
| Slovakia |
| Belarus |
| Chile |
| Colombia |
| Czech Republic |
| Estonia |
| Georgia |
| Germany |
| India |
| Kazakhstan |
| Latvia |
| Spain |
| Macedonia, the former Yugoslav Republic of |
| Mexico |
| Moldova, Republic of |
| Peru |
| Poland |
| Russian Federation |
| Serbia |
| Turkey |
| Ukraine |
| United Kingdom |
| United States |
|
| 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
|
| Last visit of the last patient |
|
| 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 | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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