Multiple sclerosis MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Simvastatin 40 mg film-coated tablets
Product Name: Simvastatin 40 mg film-coated tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: Simvastatin
Concentration unit: mg milligram(s)
C
Sponsors
University College London Comprehensive Clinical Trials Unit
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with a confirmed diagnosis of multiple sclerosis (MS) that have entered the secondary progressive stage at randomisation. Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years. Progression can be evident from either an increase of at least one point on the Expanded Disability Status Scale (EDSS), or clinical documentation of increasing disability 2. EDSS 4.0 - 6.5 (inclusive) 3. Aged 25 to 65 years old 4. Male or Female 5. Patients must be able and willing to comply with the terms of this protocol. 6. Written informed consent provided 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 1180 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Relapse within 3 months of baseline visit 2. Patients that have been treated with steroids (intravenous and/or oral) due to MS relapse/progression within 3 months of baseline visit. These patients may undergo a further screening visit once the 3 month window has expired and may be included if no steroid treatment has been administered in the intervening period (Note: Patients on steroids for another medical condition may be included in the trial provided the steroid prescription is not for MS relapse/progression) 3. Significant organ co-morbidity e.g. cardiac failure, renal failure, malignancy 4. Screening levels of alanine aminotransferase (ALT) / aspartate aminotransferase (AST) or creatinine kinase (CK) = 3x upper limit of normal (ULN) 5. Current use of a statin; or any use within the last 6 months 6. Medications that interact unfavourably with simvastatin as outlined in the current summary of product characteristics (SmPC); including but not limited to CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, posaconazole, voriconazole, fluconazole, HIV protease inhibitors (e.g. nelfinavir), boceprevir , erythromycin, clarithromycin, telithromycin, telaprevir, nefazodone, fibrates (including fenofibrates), nicotinic acid ( or products containing niacin), azole anti-fungal preparations, macrolide antibiotics, protease inhibitors, verapamil, amiodarone, amlodipine, gemfibrozil, ciclosporin, danazol , diltiazem, rifampicin , fusidic acid, grapefruit juice or alcohol abuse 7. Primary progressive MS 8. Diabetes Mellitus Type 1 9. Uncontrolled hypothyroidism 10.Female participants that are pregnant or breast feeding. Women of child bearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period, and up to 4 weeks after the last dose of study drug. 11. Use of immunosuppressants (e.g. azathioprine, methotrexate, ciclosporine) or disease modifying treatments (avonex, rebif, betaferon, glatiramer) within the previous 6 months. 12. Use of mitoxantrone, natalizumab, alemtuzumab, daclizumab or other monoclonal antibody treatment, if treated within the last 12 months. 13. Use of fingolimod, fumarate, teriflunomide within the last 12 months. 14. Use of other experimental disease modifying treatment within the last 6 months 15. Commencement of Fampridine = 6 month from day of randomisation 16. Concurrent participation in another clinical trial of an investigational medicinal product or medical device
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the effect of daily use simvastatin (80mg) versus placebo on disability progression at 6 monthly intervals in patients with Secondary Progressive MS (SPMS). Disability progression will be assessed based on change in Expanded Disability Status Scores (EDSS) compared to baseline. The hypothesis is that repurposed simvastatin (80mg) is a disease modifying treatment for patients with SPMS. ;Secondary Objective: To further examine the clinical effects of neuroprotection following daily use of simvastatin (80mg) in patients with Secondary Progressive MS (SPMS) This will be assessed using clinician and patient reported outcome measures in both treatment groups. To estimate the incremental cost and cost-effectiveness of simvastatin versus standard care for the trial period and for the lifetime horizon.;Primary end point(s): The primary outcome measure is the time to initial disability progression between the simvastatin and placebo arm based on the Expanded Disability Status Scale (EDSS) measured on a 6 monthly basis from baseline until last available EDSS score recorded at last attended clinic appointment /via telephone. The initial disability progression event is finalised as positive if disability is sustained and confirmed =6 months later. *Participants presenting with an initial disability progression (based on EDSS scores) at visit 10 clinic follow up with less than 6 months to the end of trial may have the event finalised as positive 3-6 months later.;Timepoint(s) of evaluation of this end point: As per protocol. Time point – EDSS will be measured on a 6 monthly basis from baseline until last available EDSS score recorded at last attended clinic appointment /via telephone. Visit 2 - Baseline/Randomisation (M0/week 0) Visit 5 - (M6/week 26) Visit 6 - (M12/week 52) Visit 7 - (M18/week 78) Visit 8 - (M24/week 104) Visit 9 - (M30/week 130) Visit 10 - (M36/week 156)# #Participants with an initial disability p | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Examine clinical effects of neuroprotection as measured by clinician and patient reported outcome measures in both treatment groups. Time to disability progression will be evaluated for a composite measure of disability progression: =20% increase in time taken to complete T25FW, or =20% increase in time to complete 9HPT, or increase in EDSS (0.5 point increase if baseline =6 /1.0 point increase if baseline <6). Each component of the composite outcome measure will also be examined using time to event analysis 2. To estimate the incremental cost and cost-effectiveness of simvastatin versus standard care for the trial period and for the lifetime horizon; ;Timepoint(s) of evaluation of this end point: As per protocol. Visit 2 - Baseline/Randomisation (M0/week 0) Visit 5 - (M6/week 26) Visit 6 - (M12/week 52) Visit 7 - (M18/week 78) Visit 8 - (M24/week 104) Visit 9 - (M30/week 130) Visit 10 - (M36/week 156)# #Participants with an initial disability progression based on EDSS scores recorded at visit 10 will have an additional appointment scheduled up to 6 months later. Participants will continue taking trial medication until their next clinic follow up appointment. Visit 11- (M42/week 182) | — |
Countries
United Kingdom
Contacts
Public ContactChief Investigator
University College London
Outcome results
None listed