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.

Phase 2

• Conditions: MS; Multiple sclerosis; 10012303

• Registration Number: NL-OMON49976
• Lead Sponsor: Vrije Universiteit Medisch Centrum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 100

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).

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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The change in whole brain atrophy rate, comparing rates during 6-month run-in<br /><br>period to 18-month treatment period. </p><br>

Secondary Outcome Measures

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