Primary progressive multiple sclerosis. MedDRA version: 17.1 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General inclusion criteria: 1. male or female 2. 25 through 65 years of age inclusive 3. females of childbearing potential must: • have a negative pregnancy test at Baseline (prior to randomization) and • use simultaneously two forms of effective contraception during the treatment and 3-months after discontinuation of study medication (refer to Section 7.5.9 for details) 4. sign written informed consent prior to participating in the study Primary Progressive Multiple sclerosis / specific inclusion criteria : 1. diagnosis of primary progressive multiple sclerosis (according to the 2005 Revised McDonald criteria, Appendix 8): • one year of disease progression plus • two of the following: - positive brain MRI (nine T2 lesions or four or more T2 lesions with positive visual evoked potential) - positive spinal cord MRI (2 focal T2 lesions), - positive CSF • Central review of the diagnostic criteria for PPMS will b erequired prior to randomization (refer to Appendix 9 for details). 2. duration of disease at Baseline • time since first reported symptoms between 2 and 10 years 3. documented evidence of clinical disability progression in the 2 years prior to Screening • clinical disability progression should have been observed in each of the previous 2 years prior to Screening as per clinical judgment of the investigator. • in addition, disability progression must be documented by an increase in the EDSS score of at least 0.5 points at any time point during the 2 years prior to Screening. Should documented EDSS scores not be available, a written summary of the clinical evidence of disability progression in the previous 2 years must be submitted for central review. 4. disability status at Screening (V1 or V2) • EDSS score of 3.5-6.0 inclusive • pyramidal functional system score of 2 or more • 25’TWT less than 30 seconds Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. history of MS attack/relapse as per clinical judgement of the investigator 2. progressive disabling neurological disorder, other than PPMS 3. pure cerebellar progressive syndrome or pure visual progressive syndrome or a pure cognitive progressive syndrome 4. presence of cervical spinal cord compression on Screening MRI 5. relevant history of vitamin B12 deficit 6. history of chronic active disease of the immune system other than MS which may require systemic immunosuppressive treatment or a known immunodeficiency syndrome 7. history or presence of malignancy (except for successfully treated basal or squamous cell carcinoma of skin) 8. known or ‘new’ diagnosis of diabetes mellitus (if Screening blood glucose is suspicious for diabetes [=126 mg/dL or =7 mmol/L if fasting and =200 mg/dL or 11.1 mmol/L if random testing] a patient should be further evaluated for diabetes mellitus) 9. diagnosis of macular edema during Pre-randomization Phase (patients with a history of macular edema will be allowed to enter the study provided that they do not have macular edema at the ophthalmic Screening visit) 10. evidence of syphilis, borreliosis, HIV, Hepatitis B, Hepatitis C infection or any other active systemic bacterial, viral or fungal infections 11. have received total lymphoid irradiation or bone marrow transplantation 12. have been treated with: • systemic corticosteroids or adrenocorticotropic hormones (ACTH) within 3 months prior to randomization • interferon-beta (IFN-*) or glatiramer acetate within 3 months prior to randomization • immunosuppressive medications such as azathioprine or methotrexate within 6 months prior to randomization • immunoglobulins and/or monoclonal antibodies within 6 months prior to randomization • any mitoxantrone during previous 5 years prior to randomization or evidence of cardiotoxicity following mitoxantrone or mitoxantrone at a total cumulative life-time dose of more than 60 mg/m2 • cladribine, cyclophosphamide at any time 13. any medically unstable condition, as assessed by the primary treating physician 14. any of the following cardiovascular conditions (see enclosed protocol section 5.2) 15. any of the following pulmonary conditions (see enclosed protocol section 5.2) 16. any of the following hepatic conditions (see enclosed protocol section 5.2) 17. any of the following abnormal laboratory values (see enclosed protocol section 5.2) 18. history of substance abuse (drug or alcohol) or any other factor (i.e., serious psychiatric condition) that may interfere with the subject’s ability to cooperate and comply with the study procedures 19. unable to undergo MRI scans, including claustrophobia or history of hypersensitivity to gadolinium-DTPA 20. participation in any clinical research study evaluating another investigational drug or therapy within 6 months prior to randomization 21. pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. 22. negative for varicella-zoster virus IgG antibodies at Screening 23. have received any live or live attenuated vaccines (including for varicella-zoster virus or measles) within 2 months prior to randomization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of 0.5mg fingolimod relative to placebo on delaying the time to sustained disability progression.;Secondary Objective: • To evaluate the effect of 0.5mg fingolimod relative to placebo on delaying the time to 3-month sustained disability progression as measured by the EDSS. • To evaluate the effect of fingolimod 0.5mg relative to placebo on the percent change from baseline in brain volume. ;Primary end point(s): The primary endpoint is the time to sustained disability progression, which is defined based on three types of events for each subject: • 3-month sustained increase of at least 20% from Baseline in the time taken to complete the 25’TWT or • 3-month sustained increase from Baseline in the EDSS score (1 point in patients with Baseline EDSS score 3.5 to 5.0; 0.5 point in patients with Baseline EDSS score of 5.5 or 6.0) or • 3-month sustained increase of at least 20% from Baseline in the time taken to complete the 9-HPT in either one of the hands (dominant or non-dominant) Disability progression in this study can be achieved by the occurrence of any of three events (sustained disability progression on 25’TWT, EDSS or 9-HPT) for each subject (See enclosed protocol for further details, section 10.4.). In addition, primary efficacy analysis will be based on data from the 654 newly-randomized patients following implementation of FTY720D2306 Protocol Amendment 5 and the placebo patients randomized prior to that. ;Timepoint(s) of evaluation of this end point: 36 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate the effect of fingolimod 0.5 mg relative to placebo on delaying the time to 3-month sustained disability progression as measured by the EDSS To evaluate the effect of fingolimod 0.5 mg relative to placebo on the percent change from baseline in brain volume.;Timepoint(s) of evaluation of this end point: 36 months | — |
Countries
Australia, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Netherlands, Poland, Russian Federation, South Africa, Spain, Sweden, Switzerland, Turkey, United Kingdom
Contacts
Public ContactInformacní služba - klin. hodnocení
Novartis s.r.o.
Outcome results
None listed