E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
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 evolution of walking capacity as measured by T100T, T25FW, MWD and EDSS during the first year of therapy with natalizumab |
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E.2.2 | Secondary objectives of the trial |
To evaluate the correlation between the MWD and EDSS and both walking tests, the T100T and the T25FW at baseline, at 6 months and at 1 year of therapy.
To determine how well each of the walking tests, T100T or T25FW, predicts walking limitations in all subjects and in the subgroups of subjects stratified by baseline EDSS. |
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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 provide all authorizations required by local law (e.g., Protected Health Information [PHI]) 2. Men or women between 18 and 60 years of age, inclusive 3. Must have EDSS ≤ 5.5 at baseline. 4. Must be able to walk at least 100m without assistive devices 5. Must be natalizumab naïve 6. Must have a documented diagnosis of a relapsing remitting form of MS as defined by the revised McDonald Committee criteria (Polman, 2005) 7. Must have had a recent MRI (within 3 months from baseline) 8. Must have had at least 1 relapse in the previous year and must satisfy the locally approved therapeutic indications for TYSABRI®. If TYSABRI® is not yet approved in a specific country, patients must fulfill the following criteria: • Patients with high disease activity despite treatment with a beta-interferon defined as patients who have failed to respond to a full and adequate course of a beta-interferon. Patients must have had at least 1 relapse in the previous year while on therapy, and have at least 9 T2-hyperintense lesions in cranial MRI or at least 1 Gd-enhancing lesion. Or • Patients with rapidly evolving severe relapsing remitting multiple sclerosis defined as patients who have had 2 or more disabling relapses in one year and 1 or more Gd-enhancing lesions on brain MRI or significant increase in T2 lesions as compared to a previous MRI 9. Must be stable in disability for at least 30 days prior to enrollment to the study 10. Must be stable in symptomatic management of the disease, specifically spasticity, depression and fatigue for at least 30 days prior to enrollment to the study 11. Must be considered by the Investigator to be free of signs and symptoms suggestive of PML based on medical history, physical examination, or laboratory testing. 12. Must be willing to discontinue and remain free from concomitant immunosuppressive or immunomodulatory treatment (including IFN beta and GA) while being treated with natalizumab during the study
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E.4 | Principal exclusion criteria |
Medical History: 1. Onset of a relapse within 50 days prior to first infusion 2. Considered by the Investigator to be immunocompromised, based on medical history, physical examination, or laboratory testing or due to prior immunosuppressive treatment 3. History of, or available abnormal laboratory results indicative of, any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric (including major depression), renal, and/or other major disease that would preclude the administration of a recombinant humanized antibody immunomodulating agent. The Investigator must re-review the subject’s medical fitness for participation and consider any diseases that would preclude treatment. 4. History of malignancy (subjects with basal cell carcinoma that has been completely excised prior to study entry remain eligible) 5. Known history of human immunodeficiency virus infection or hematological malignancy 6. History of organ transplantation (including anti-rejection therapy) 7. A clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to the Screening Visit.
Treatment History: 8. Treatment with immunosuppressant medications (e.g., mitoxantrone, cyclophosphamide, cyclosporine, azathioprine, methotrexate) within 6 months prior to Screening
Miscellaneous 9. Female subjects who are not postmenopausal for at least 1 year, surgically sterile (does not include tubal ligation), or willing to practice effective contraception (as defined by the Investigator) during the study 10. Women who are breastfeeding, pregnant, or planning to become pregnant while on study 11. Current enrollment in any other study treatment or disease study 12. 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 subject's ability to comply with the study protocol 13. Subjects with walking impairment due to causes other than MS 14. Other unspecified reasons that, in the opinion of the Investigator and/or Biogen Idec, make the subject unsuitable for enrollment into this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the evolution of walking abilities as measured by MWD, EDSS, T25FW and T100T during the first year of therapy with natalizumab. |
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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 | No |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 8 |
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 | 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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End of study is defined as last patient last visit, which is defined as the week 52 telephone follow up |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |