Research on the effect of add-on high dosage simvastatin treatment on progression in MS patients treated with ocrelizumab and natalizumab.

• Register: EUCTR
• Last refreshed on: 6 July 2020
• Main ID: EUCTR2019-003127-38-NL
• Date of registration: 09/04/2020
• Prospective Registration: Yes
• Primary sponsor: VUmc Neurology Department
• Public title: Research on the effect of add-on high dosage simvastatin treatment on progression in MS patients treated with ocrelizumab and natalizumab.
• Scientific title: Efficacy of add-on high dose simvastatin on markers for disease progression in MS patients treated with ocrelizumab and natalizumab (SIMSON), a phase II clinical trial. - SIMSON trial
• Date of first enrolment: 09/04/2020
• Target sample size: 100
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-003127-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Run-in versus treatment; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: Investigators Office
• Affiliation: MS Center Amsterdam

• Name: Investigators Office
• Affiliation: MS Center Amsterdam

Key inclusion & exclusion criteria

Inclusion criteria:
1. Definite diagnosis of multiple sclerosis (MS) according to the revised McDonald 2017 criteria.
2. Treatment with ocrelizumab or natalizumab for at least 6 months prior to inclusion.
4. Age 18 to 65 years old.
5. EDSS score 3.0 – 7.0 (inclusive).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. MS relapse within 6 months of baseline visit, with or without treatment with steroids.
2. Use of immunomodulation or -suppression other than ocrelizumab or natalizumab within the previous 6 months.
3. Commencement of treatment with fampridine within 3 months of baseline visit.
4. Concomitant use of lipid lowering drugs or use within 6 months before baseline visit.
5. Concomitant use of potent CYP3A4 inhibitors.
6. (History of) hypersensitivity, muscular toxicity or other adverse reaction due to statin or fibrate use.
7. Any predisposing factor to rhabdomyolysis: renal impairment (creatinine clearance <70 mL/min), uncontrolled hypothyroidism, personal or familial history of hereditary muscular disorders, alcohol abuse (>14 standard drinks units per week).
8. Baseline serum creatine kinase (CK) levels of >5 x ULN (confirmed by second measurement within 5-7 days), or at least 3-fold increase from baseline with associated muscle symptoms.
9. Active liver disease or unexplained persistent elevations of serum transaminases 3 x ULN.


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

Health Condition(s) or Problem(s) studied

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

Multiple sclerosis

Intervention(s)

Product Name: Simvastatin
Pharmaceutical Form: Tablet
INN or Proposed INN: SIMVASTATIN
Current Sponsor code: SIMSON71001
Other descriptive name: Simvastatine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Main Objective: To assess the efficacy of add-on high-dose simvastatin in MS patients treated with natalizumab or ocrelizumab for at least six months on whole brain atrophy rate.

Primary end point(s): The change in whole brain atrophy rate, comparing rates during 6-month run-in period to 18-month treatment period.

Secondary Objective: 1. To investigate the effect of add-on high-dose simvastatin in the above mentioned patient population on regional grey and white matter volumes.
2. To explore the potential of serum NfL as predictor of treatment response and disease progression.
3. To investigate the effect on clinical, other imaging and patient reported outcome measures of disability progression of add-on high-dose simvastatin treatment.
4. To assess safety and tolerability of simvastatin add-on to NTZ or OCR treatment.
5. To explore differences in efficacy on the described measures between subgroups based on demographics, MS subtype or disease modifying therapy.

Timepoint(s) of evaluation of this end point: - Baseline (month 0)
- End of 6-month run-in period (month 6)
- After 6 month of simvastatin treatment (month 12)
- End of study (month 24)

Secondary Outcome(s)

Secondary end point(s): Secondary outcome measures include clinical outcome measures (neurological exam, arm- and walking functions, cognitive functions), biochemical outcome measures (sNfL, multi-parameter analysis of peripheral blood mononuclear cells (PBMC) and serum cholesterol), other imaging outcome measures (regional white and gray matter atrophy rate, functional connectivity on brain MRI, OCT), patient-reported outcome measures (questionnaires on the impact of MS on arm function, walking function, neuropsychological status and quality of life) and safety and tolerability (incidence of (serious) adverse events, CK levels).

Timepoint(s) of evaluation of this end point: Clinical testing (EDSS, MSFC, BICAMS, 6MWTEC), OCT and questionnaires are performed at baseline, month 6, month 12 and month 24. Biochemical measures including serum NfL are measured at baseline, month 6, month 7 and every 3 months between month 9 and 24. Adverse events survey is collected at baseline, month 6, month 7, every 3 months between month 9 and 24.

Secondary ID(s)

NL71001.029.19

Source(s) of Monetary Support

Stichting MS Research

Ethics review

Status: Approved
Approval date: 24/03/2020
Contact: