Relapsing-Remitting Multiple Sclerosis MedDRA version: 14.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: TYSABRI
Product Name: Natalizumab for IV Infusion
Product Code: AN100226
BG00002
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: NATALIZUMAB
CAS Number: 189261-10-7
Current Sponsor code: AN100226
BG00002
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intra
BG00002
Pharmaceutical Form: Solution for injection
INN or Proposed INN: NATALIZUMAB
CAS Number: 189261-10-7
Current Sponsor code: AN100226
BG00002
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subc
Sponsors
Biogen Idec Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 55 years old, inclusive, at the time of informed consent. 3. Subjects of childbearing potential must practice effective contraception during the study. 4. A documented diagnosis of RRMS. 5. Free of MS relapse, as determined by the enrolling Investigator, for 12 months prior to randomization. 6. Treatment with natalizumab according to locally approved pescribing information for a minimum of the 12 months immediately prior to randomization. The subject must have received at least 11 doses of natalizumab in the 12 months prior to randomization with no missed doses in the 3 months prior to randomization. 7. In the 12 months prior to the initiation of natalizumab, subject must have experienced a minimal level of disease activity as defined by: • 2 or more documented clinical relapses OR • 1 relapse and documented MRI activity, defined by the presence of at least one Gd enhancing lesion on MRI, unrelated to the relapse. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Known history of Human Immunodeficiency Virus (HIV). 2. Known history of hepatitis C (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]). 3. Positive for anti-natalizumab antibodies at Screening. 4. MRI positive for Gd-enhancing lesions at study entry. 5. Subjects for whom MRI is contraindicated, e.g., have a pacemaker or other contraindicated implanted metal devices, have suffered, or are at risk for, side effects from 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 (including diabetes), urologic, pulmonary, neurologic (except for RRMS), dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical study. 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. History of transplantation or any anti-rejection therapy. 9. History of severe allergic or anaphylactic reactions or known hypersensitivity to any drug. 10. A clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days prior to Screening, or PML or other opportunistic infections at any time. 11. Signs or symptoms suggestive of any serious infection, based on medical history, physical examination, or laboratory testing, as determined by the Investigator. MS Treatment History 12. Prior treatment with total lymphoid irradiation. 13. Prior treatment with cladribine, mitoxantrone, fingolimod, T-cell or T-cell receptor vaccination, cyclophosphamide, cyclosporine, azathioprine, methotrexate, mycophenolate mofetil, or any therapeutic monoclonal antibody other than natalizumab within 24 months prior to randomization. 14. Prior treatment with intravenous immunoglobulin (IVIg), plasmapheresis, or cytapheresis within 12 months prior to randomization. 15. Treatment with IV or oral corticosteroids (topical corticosteroids are acceptable) or related products within 3 months prior to randomization. Miscellaneous 16. Female subjects considering becoming pregnant while in the study. 17. Female subjects who are pregnant or currently breastfeeding. 18. History of drug or alcohol abuse within 2 years prior to entry per Investigator judgment. 19. 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. 20. Receiving any other investigational treatment within the 12 months prior to Screening or concurrent with this study. 21. Any pre-scheduled elective procedure during the study period that, in the opinion of the Investigator, would interfere with study endpoints. 22. Any other condition, clinical finding, or reason that, in the opinion of the Investigator and/or the Sponsor, makes the subject unsuitable for enrollment into this study. 23. Previous participation in this study at randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • To characterize and compare PK/PD profiles across multiple dose regimens of natalizumab. • To characterize effects on secondary brain MRI measures. • To evaluate potential laboratory markers of immune function and trafficking across the treatment regimens. • To assess the safety and tolerability across multiple dose regimens.;Primary end point(s): Cumulative number of combined unique active lesions (sum of the number of new Gd enhancing and new or newly enlarging T2 hyperintense lesions not associated with Gd enhancement on T1 weighted scans) based on brain MRI scans.;Timepoint(s) of evaluation of this end point: At weeks 12, 24, 36, 48 and 60.;Main Objective: To explore the effects of multiple regimens of natalizumab on disease activity and safety in subjects with relapsing remitting MS. | — |
Countries
Belgium, Germany, Italy, Spain
Outcome results
None listed