MS-STAT2 - Multiple Sclerosis – Simvastatin Trial 2

• Register: EUCTR
• Last refreshed on: 26 November 2018
• Main ID: EUCTR2017-003328-56-GB
• Date of registration: 31/10/2017
• Prospective Registration: Yes
• Primary sponsor: University College London Comprehensive Clinical Trials Unit
• Public title: MS-STAT2 - Multiple Sclerosis – Simvastatin Trial 2
• Scientific title: A phase 3 randomised, double blind, clinical trial investigating the effectiveness of repurposed simvastatin compared to placebo, in secondary progressive multiple sclerosis, in slowing the progression of disability - MS-STAT2
• Date of first enrolment: 19/12/2017
• Target sample size: 1180
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003328-56
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Chief Investigator
• Affiliation: University College London

• Name: Chief Investigator
• Affiliation: University College London

Key inclusion & exclusion 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:
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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple sclerosis
MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

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)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Simvastatine Sandoz 40 mg filmomhulde tabletten
Product Name: Simvastatine Sandoz 40 mg filmomhulde tabletten
Pharmaceutical Form: Tablet
INN or Proposed INN: Simvastatin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Trade Name: SimvaHEXAL® 40 mg Filmtabletten
Product Name: SimvaHEXAL® 40 mg Filmtabletten
Pharmaceutical Form: Tablet
INN or Proposed INN: Simvastatin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Trade Name: Simvastatina Sandoz 40 mg comprimidos recubiertos con película EFG
Product Name: Simvastatina Sandoz 40 mg comprimidos recubiertos con película EFG
Pharmaceutical Form: Tablet
INN or Proposed INN: Simvastatin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Trade Name: Sinvastatina Sandoz 40 mg comprimidos revestidos por película
Product Name: Sinvastatina Sandoz 40 mg comprimidos revestidos por película
Pharmaceutical Form: Tablet
INN or Proposed INN: Simvastatin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Trade Name: Sivatin 40 mg film-coated tablets
Product Name: Sivatin 40 mg film-coated tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: Simvastatin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Trade Name: Simvastatine Sandoz 40mg deelbare filmomhulde tabletten
Product Name: Simvastatine Sandoz 40mg deelbare filmomhulde tabletten
Pharmaceutical Form: Tablet
INN or Proposed INN: Simvastatin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentrat

Primary Outcome(s)

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.

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 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)

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.

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.

Secondary Outcome(s)

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)

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;

Secondary ID(s)

CTU/2014/107

ISRCTN82598726

Source(s) of Monetary Support

National Institute for Health Research - Health Technology Assessment