| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsing-Remitting Multiple Sclerosis |
|
| E.1.1.1 | Medical condition in easily understood language |
Multiple sclerosis characterized by unpredictable relapses followed by
periods with no new signs of disease activity |
|
| 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 | 14.0 |
| 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 |
|
| 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 provide study treatment
in fulfillment of the commitments made in previous versions of the
protocol. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Have signed written informed consent (in person or through guardian) to participate in the study and provided written authorization to use protected health information in accordance with local laws.
2. Have a diagnosis of relapsing remitting multiple sclerosis as defined by the revised McDonald Committee criteria (Polman 2005).
3. Must have been treated with a stable regimen of either glatiramer acetate (20 mg per day SC) or interferon β-1a (44 mcg 3 times per week) as their principal first therapy for MS for 6 to 25 months prior to screening. (Note: prior treatment with another MS therapy of ≤30 days total duration is not exclusionary [e.g., titration to 44 mcg is allowed]).
4. Have shown evidence of disease activity within 12 months prior to screening while on therapy. Disease activity must be observed after a minimum of 6 months of treatment, but before 25 months of treatment. Disease activity is defined as:
• One or more clinical relapses (Relapses must occur after 6 months of treatment, but before 25 months of treatment)
AND/OR
• Two or more new MRI lesions (Gd+ and/or T2 hyperintense) observed on an MRI scan. Qualifying lesions must be observed on scans performed after 6 months of treatment, but before 25 months of treatment. These qualifying scans must support at least one of the following:
a. ≥2 Gd+ lesions on MRI scan(s)
b. ≥2 new T2 hyperintense lesions observed on an MRI scan when compared with a *baseline MRI scan
c. ≥1 Gd+ lesion and ≥1 new T2 hyperintense lesion observed on an MRI scan when compared with a *baseline MRI scan
* A baseline MRI scan is an MRI scan performed at the initiation of therapy (±6 weeks) that is compared with subsequent MRI scans to determine if new T2 hyperintense lesions are observed. If this baseline scan at initiation of therapy is not available, any scan performed after initiation of therapy may be used as the baseline MRI. New T2 MRI activity must be verified by the central reader center.
5. Be naïve to natalizumab.
6. Be between the ages of 18 and 60, inclusive at the time of informed consent.
7. Have a documented EDSS score between 0.0 and 5.5, inclusive.
|
|
| E.4 | Principal exclusion criteria |
1. Have a diagnosis of 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. Patients with these conditions may also have superimposed relapses, but are distinguished from relapsing-remitting patients by the lack of clinically stable periods or clinical improvement.
2. Have known intolerance, contraindication to, or history of non-compliance with, the use of glatiramer acetate or interferon β-1a.
3. Have had an MS exacerbation (relapse) within 30 days prior to randomization AND/OR the patient has not stabilized from a previous relapse, in the opinion of the Investigator, prior to randomization.
4. The patient is considered by the Investigator to be immunocompromised based on medical history, physical examination, laboratory testing, or due to prior immunosuppressive or immunomodulating treatment.
5. Subjects for whom MRI is contraindicated, i.e., have pacemakers or other contraindicated implanted metal devices, have suffered or are at risk for side effects from gadolinium (Gd), or have claustrophobia that cannot be medically managed.
6. History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical trial.
7. 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).
8. Known history of Human Immunodeficiency Virus (HIV).
9. Positive test result for Hepatitis C virus (test for hepatitis C virus antibody [HCV Ab]) or hepatitis B virus (test for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]).
10. History of transplantation or any anti-rejection therapy.
11. History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
12. A clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to screening.
13. History of PML.
14. Prior treatment with total lymphoid irradiation, cladribine, mitoxantrone, fingolimod, T-cell or T-cell receptor vaccination, cyclophosphamide, cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, or any therapeutic monoclonal antibody, including natalizumab or rituximab.
15. Prior treatment with intravenous immunoglobulin (IVIg), plasmapheresis or cytapheresis within 6-months prior to randomization.
16. Treatment with IV or oral corticosteroids within 30 days of randomization.
17. Treatment with 4-aminopyridine for subjects in countries where marketing authorization has not been obtained. Treatment with compounded formulations of 4-aminopyridine is prohibited for all subjects.
18. Treatment with an approved formulation of 4-aminopyridine (i.e., fampridine-SR,
dalfampridine, or Ampyra) for ≤90 days prior to randomization in countries where marketing authorization has been obtained.
19. Female subjects considering becoming pregnant while in the study.
20. Female subjects of childbearing potential who have a positive pregnancy test at either the Screening Visit or the Day 0 (Baseline) Visit.
21. Female subjects who are pregnant or currently breastfeeding.
22. History of drug or alcohol abuse within 2 years prior to entry.
23. Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the patient's ability to comply with the study protocol.
24. Received an investigational treatment within the 6 months prior to randomization. Concurrent participation in another study, such as observational or non-interventional studies, must be pre-approved by the Sponsor on a case-by-case basis.
25. Patient with any pre-scheduled elective procedure during the study period that, in the opinion of the Investigator, would interfere with trial parameters.
26. Patient with any other condition, clinical finding, or reason that, in the opinion of the Investigator and/or the Sponsor, is determined to be unsuitable for enrollment into this study.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 13 |
| 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 |
|
| 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
|
|
| 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 | 8 |
| 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 | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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