Multiple Sclerosis-Simvastatin Trial 2

Prior treatment

• Patients that have been treated with steroids (intravenous and/or oral) due to MS relapse/progression within 3 months from the final day of relapse to the 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)
• 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;
• Use of immunosuppressants (e.g. azathioprine, methotrexate, ciclosporine) or disease modifying treatments (avonex, rebif, betaferon, glatiramer) within the previous 6 months;
• Use of mitoxantrone, natalizumab, alemtuzumab, daclizumab or other monoclonal antibody treatment, if treated within the last 12 months;
• Concurrent participation in another clinical trial of an investigational medicinal product or medical device;

Other illness

• Significant organ co-morbidity e.g. cardiac failure, renal failure, malignancy;
• 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, clrithromycin, 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, elbasvir, grazoprevir,ticagrelor, daptomycin, grapefruit juice or alcohol abuse;
• Diabetes mellitus type 1;
• Use of other experimental disease modifying treatment within the last 6 months;

Lab values

• Screening levels of alanine aminotransferase (ALT) / aspartate aminotransferase (AST) or creatine kinase (CK) ≥3 x upper limit of normal (ULN);
• Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

Other

• Relapse within 3 months of baseline visit. Patients will be eligible where 3 months from the final day of the relapse, has elapsed by the date of the baseline visit;
• Current use of a statin; or any use within the last 6 months;
• Primary progressive MS;
• Uncontrolled hypothyroidism;
• Use of fingolimod, dimethyl fumarate, teriflunomide, cladribine within the last 12 months;
• Commencement of fampridine ≤6 months from day of randomisation;

• Patients with a confirmed diagnosis of multiple sclerosis (MS) that have entered the secondary progressive stage. 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 1 point if EDSS score \<6, or an increase of 0.5 point if EDSS score ≥6, or clinical documentation of increasing disability;
• EDSS 4.0 - 6.5 (inclusive);
• Aged 25 to 65 years old;
• Patients must be able and willing to comply with the terms of this protocol;
• Written informed consent provided.