Later phase MS SPMS
Conditions
Interventions
An IV infusion of either natalizumab or matching placebo will be added in
clinic by a study nurse monthly for 96 weeks (approximately 2 years).
Afterwards, if the patient decides to participate in
Sponsors
Biogen Idec Limited
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Part 1: To be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of randomization (Day 0), or at the timepoint specified in the individual eligibility criterion listed:;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. Be between the ages of 18 and 58, inclusive, at the time of informed consent.;3. Onset of SPMS at least 2 years prior to enrollment. SPMS is defined as relapsing-remitting disease followed by progression of disability independent of or not explained by MS relapses (Lublin, Reingold, 1996) ) for at least 2 years. ;4. Have EDSS score of 3.0 to 6.5, inclusive.;5. Have an MS Severity Score (MSSS) of 4 or higher.;6. Have documented confirmed evidence of disease progression independent of clinical relapses over the 1 year prior to enrollment as defined in the Study Reference Guide.;7. Subjects must have completed those baseline assessments associated with components of the primary endpoint (EDSS, T25FW, 9HPT) prior to randomization (Day 0).;8. 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 infusion.;Part 2: To be eligible to participate in the Part 2 Extension Phase of this study, candidates must meet the folowing eligibility criteria at the time of consent into Part 2, or at the timepoint specified in the individual eligibility criterion listed:;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. Subjects must have participated in Part 1, have documented Week 108 assessment attempts for EDSS, T25FW, and 9HPT prior to first open-label dosing at Week 108 and not have missed 2 or more consecutive infusions in Part 1 of the study.;3. 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 infusion.
Exclusion criteria
Exclusion criteria: Part 1: Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of randomization (Day 0), or at the timepoint specified in the individual criterion listed:;1.Have a diagnosis of RRMS or primary progressive MS as defined by the revised McDonald Committee criteria (Polman et al 2005).;2. Had a recent clinical relapse (within 3 months) prior to randomization. ;3. Have a T25FW test of >30 seconds during the screening period.;4. Any value below the lower limit of normal for blood levels of leukocytes, lymphocytes, or neutrophils.;5. Considered by the Investigator to be immunocompromised based on medical history, physical examination, laboratory testing, or any other testing required by local guidelines, or due to prior immunosuppressive or immunomodulating treatment.;6. Subjects for whom MRI is contraindicated (i.e., have pacemakers or other contraindicated implanted metal devices or have claustrophobia that cannot be medically managed).;7. History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (other than MS), dermatologic, psychiatric, and renal, or other major disease that would preclude participation in a clinical study.;8. 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).;9. Known history of or positive test result for Human Immunodeficiency Virus (HIV).;10. 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]).;11. History of transplantation or any anti-rejection therapy.;12. Presence of any infectious disease (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to screening.;13. History of PML or other opportunistic infections including active tuberculosis.;Treatment History;14. Any prior treatment with cell-depleting therapies, including total lymphoid irradiation, cladribine, rituximab, alemtuzumab, or bone marrow ablation.;15. Any prior treatment with natalizumab. ;16. Treatment with mitoxantrone, cyclophosphamide, cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, T cell or T cell receptor vaccination, fingolimod, daclizumab, or cytapheresis within 6 months prior to randomization.;17. Treatment with IV or oral corticosteroids, intravenous immunoglobulin (IVIg), or plasmapheresis for treatment of MS within the 3 months prior to randomization.;18. Treatment with glatiramer acetate or any interferon beta preparations within 4 weeks prior to randomization.;19. Treatment with 4-aminopyridine 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.;Miscellaneous;20. Female subjects considering becoming pregnant while in the study. ;21. Female subjects of childbearing potential who have a positive pregnancy test at either the Screening Visit or Week 0.;22. Female subjects who are pregnant or currently breastfeeding. ;23. History of drug or alcohol abuse, in the opinion of the Investigator, within 2 years prior to entry.;24. Unwillingness or inability to comply with the requirements of this protocol, includi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is a binary outcome of confirmed progressors or non-progressors at study end. The percentage of confirmed progressors will be presented by treatment group, with the treatment comparison analyzed by the logistic regression model. The percentage of confirmed progressors in each of EDSS, T25FW, and 9HPT will also be presented with treatment comparisons by the logistic regression model. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints will be summarized by presenting summary statistics for continuous or frequency distributions for categorical variables. In general, binary outcomes will be analyzed by the logistic regression model, time to event data by the Cox proportional hazards model, count data by the negative binomial regression model or Wilcoxon rank-sum test, and continuous responses by the analysis of variance or the analysis of covariance. To maintain the overall type I error rate at 5%, a closed testing procedure will be used to adjust for multiple secondary endpoints. | — |
Countries
Netherlands
Outcome results
None listed