Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK

BMJ Open. 2024 Sep 16;14(9):e086414. doi: 10.1136/bmjopen-2024-086414.

Abstract

Introduction: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS.

Methods and analysis: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.0-6.5 (inclusive). Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years.Participants will be allocated to simvastatin or placebo in a 1:1 ratio. The active treatment will be 80 mg daily, after 1 month at 40 mg daily. 31 hospitals across the UK will participate.The primary outcome is (confirmed) disability progression at 6 monthly intervals, measured as change from EDSS baseline score. Recruitment of 1050 participants will be required to achieve a total of 330 progression events, giving 90% power to demonstrate a 30% relative reduction in disability progression versus placebo. The follow-up period is 36 months, extendable by up to 18 months for patients without confirmed progression.Clinician-reported measures include Timed 25 Foot Walk; 9 Hole Peg Test; Single Digit Modalities Test; Sloan Low Contrast Visual Acuity; Relapse assessment; modified Rankin Scale and Brief International Cognitive Assessment For Multiple Sclerosis. Patient-reported outcomes include MS-specific walking, fatigue and impact scales. A health economic analysis will occur.

Ethics and dissemination: The protocol was approved by the London-Westminster REC (17/LO/1509). This manuscript is based on protocol version 8.0, 26 February 2024. Trial findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration numbers: NCT03387670; ISRCTN82598726.

Keywords: Clinical Trial; Drug Therapy; Multiple sclerosis.

Publication types

  • Clinical Trial Protocol
  • Multicenter Study
  • Clinical Trial, Phase III

MeSH terms

  • Adult
  • Aged
  • Clinical Trials, Phase III as Topic
  • Cost-Benefit Analysis
  • Disability Evaluation
  • Disease Progression*
  • Double-Blind Method
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Multiple Sclerosis, Chronic Progressive* / drug therapy
  • Multiple Sclerosis, Chronic Progressive* / physiopathology
  • Randomized Controlled Trials as Topic
  • Simvastatin* / therapeutic use
  • Treatment Outcome
  • Vereinigtes Königreich

Substances

  • Simvastatin
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors

Associated data

  • ClinicalTrials.gov/NCT03387670