Multiple Sclerosis-Simvastatin Trial 2

Inclusion Criteria:

1. Patients with a confirmed diagnosis of multiple sclerosis (MS) that have entered thesecondary progressive stage. Steady progression rather than relapse must be themajor cause of increasing disability in the preceding 2 years. Progression can beevident from either an increase of at least 1 point if EDSS score <6, or anincrease of 0.5 point if EDSS score ≥6, or clinical documentation of increasingdisability;

2. EDSS 4.0 - 6.5 (inclusive);

3. Aged 25 to 65 years old;

4. Patients must be able and willing to comply with the terms of this protocol;

5. Written informed consent provided.

Exclusion Criteria:

1. Relapse within 3 months of baseline visit. Patients will be eligible where 3 monthsfrom the final day of the relapse, has elapsed by the date of the baseline visit;

2. Patients that have been treated with steroids (intravenous and/or oral) due to MSrelapse/progression within 3 months from the final day of relapse to the baselinevisit. These patients may undergo a further screening visit once the 3 month windowhas expired and may be included if no steroid treatment has been administered in theintervening period; (Note: Patients on steroids for another medical condition may beincluded in the trial provided the steroid prescription is not for MSrelapse/progression)

3. Significant organ co-morbidity e.g. cardiac failure, renal failure, malignancy;

4. Screening levels of alanine aminotransferase (ALT) / aspartate aminotransferase (AST) or creatine kinase (CK) ≥3 x 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 currentsummary of product characteristics (SmPC); including but not limited to CYP3A4inhibitors (e.g. itraconazole, ketoconazole, posaconazole, voriconazole,fluconazole, HIV protease inhibitors (e.g. nelfinavir), boceprevir, erythromycin,clrithromycin, telithromycin, telaprevir, nefazodone, fibrates (includingfenofibrates), nicotinic acid (or products containing niacin), azole anti-fungalpreparations, macrolide antibiotics, protease inhibitors, verapamil, amiodarone,amlodipine, gemfibrozil, ciclosporin, danazol, diltiazem, rifampicin, fusidic acid,elbasvir, grazoprevir,ticagrelor, daptomycin, 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 bearingpotential (WOCBP) who are unwilling or unable to use an acceptable method to avoidpregnancy for the entire study period, and up to 4 weeks after the last dose ofstudy drug;

11. Use of immunosuppressants (e.g. azathioprine, methotrexate, ciclosporine) or diseasemodifying treatments (avonex, rebif, betaferon, glatiramer) within the previous 6months;

12. Use of mitoxantrone, natalizumab, alemtuzumab, daclizumab or other monoclonalantibody treatment, if treated within the last 12 months;

13. Use of fingolimod, dimethyl fumarate, teriflunomide, cladribine within the last 12months;

14. Use of other experimental disease modifying treatment within the last 6 months;

15. Commencement of fampridine ≤6 months from day of randomisation;

16. Concurrent participation in another clinical trial of an investigational medicinalproduct or medical device;

17. Patients with rare hereditary problems of galactose intolerance, the Lapp lactasedeficiency or glucose-galactose malabsorption.