A three-arm, randomized, double-blind, placebo controlled, multicenter, phase II study to evaluate the efficacy of Vigantol® oil as add-on therapy in subjects with Relapsing-Remitting Multiple Sclerosis receiving treatment with Rebif®SOLARSupplementation of VigantOL® Oil versus Placebo as Add-on in Patients with Relapsing-Remitting MS receiving Rebif® treatment. - SOLAR
- Conditions
- MedDRA version: 12.1Level: LLTClassification code 10063399Term: Relapsing-remitting multiple sclerosisRelapsing-Remitting Multiple Sclerosis
- Registration Number
- EUCTR2010-020328-23-NL
- Lead Sponsor
- Merck Serono The Netherlands - a division of Merck B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 358
For inclusion in the trial, subjects with either inpatient or outpatient status must fulfill all of the following inclusion criteria by:
1. Males and females between 18 and 50 years of age.
2. Diagnosis of a relapsing-remitting form of MS, according to the revised McDonald criteria (2005).
3. Brain and/or spinal MRI with findings typical of MS.
4. A first clinical event occurring within 5 years prior to Screening.
5. Disease activity characterized by:
a) At least one MS lesion within the 12 months prior to Screening,
or
b) One or more Gd-enhancing MRI lesions within the 12 months prior to Screening.
6. EDSS score 7. Currently and for the first time treated with interferon-beta-1a (tiw) s.c., and having received this treatment for a minimum of 90 days and for not longer than 12 months before baseline visit (including titration period).
8. Willingness and ability to comply with the protocol for the duration of the trial.
9. Written informed consent given prior to any trial-related procedure not part of the normal medical practice.
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Subjects are not eligible for this trial if they fulfill any of the following exclusion criteria:
1. Pregnancy and lactation period
2. Any disease other than MS that could better explain signs and symptoms.
3. Complete transverse myelitis or bilateral optic neuritis.
4. Currently receiving or use at any time of monoclonal antibodies, mitoxantrone, cytotoxic or immunosuppressive therapy (excluding systemic steroids and adrenocorticotrophic hormone [ACTH]), B cell modulating therapies (e.g. RituxiMab or BelimuMab), total lymphoid irradiation or bone marrow transplantation.
5. Use of any cytokine or anti-cytokine therapy, intravenous immunoglobulin, plasmapheresis, or any investigational drug or experimental procedure within 12 months prior to Screening.
6. Use of oral or systemic corticosteroids or ACTH within 30 days prior to the SD1 visit.
7. Have experienced a relapse within 30 days before the SD1 visit
8. Have abnormalities of Vitamin D related hormonal system other than low dietary intake or decreased sun exposure, i.e. primary hyperparathyroidism or granulomatous disorders.
9. Have a urine calcium/creatinine (mmol/mmol) ratio greater than 1.0 or hypercalcemia (11 mg/100cc (5.5 mEq/L)).
10. Are taking medications that influence Vitamin D metabolism other than corticosteroids, i.e., phenytoin, barbiturates, thiazide diuretics and cardiac glycosides.
11. Have conditions with increased susceptibility to hypercalcemia, e.g., known arrhythmia or heart disease, treatment with Digitalis, or Hydrochlorothiazide and those who suffer from nephrolithiasis.
12. Have inadequate liver function, defined by alanine aminotransferase (ALT) > 3 times upper limit of normal (ULN), aspartate aminotransferase (AST) > 3 times ULN or alkaline phosphatase > 2.5 times ULN, or total bilirubin > 1.5 times ULN, if associated with any elevation of ALT or alkaline phosphatase
13. Moderate to severe renal impairment (estimate of glomerular filtration rate [GFR] < 50 mL/min/1.73 m2 [based on creatinine clearance according to Cockcroft-Gault equation])
14. Inadequate bone marrow reserve, defined by a WBC count < 0.5 times the lower limit of normal.
15. History or presence of serious or acute heart disease such as uncontrolled cardiac dysrhythmia or arrhythmia, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure (NYHA class 3 or 4).
16. History or presence of severe depression, history of suicide attempt, or current suicidal ideation.
17. Epilepsy or seizures not adequately controlled by treatment.
18. Current or past (within the last 2 years) alcohol or drug abuse.
19. Any major medical or psychiatric illness (such as psychosis, bipolar disorder) that in the opinion of the Investigator could create undue risk to the subject or could affect adherence with the trial protocol.
20. Known contra-indication to treatment with vitamin D (according to SPC)
21. Known hypersensitivity to IFN or its excipient(s) (according to SPC).
22. Known hypersensitivity to gadolinium.
23. Any other condition that would prevent the subject from undergoing an MRI scan.
24. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.
25. Positive HIV, hepatitis C, or hepatitis B (HBsAg and HBc antibody) serology (test performed at screening).
26. Legal incapacity or limited legal capacity.
27. Another current autoimmune disease, except diabetes.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy of Vigantol® oil versus placebo as add-on therapy in subjects with Relapsing-Remitting Multiple Sclerosis receiving treatment with Rebif®.;Secondary Objective: • To assess changes on clinical parameters.<br>• To assess changes in MRI parameters. <br>• To investigate the safety profile up to the end of the Treatment Period (Week 96), <br>• To explore pharmacogenetics/pharmacogenomics (PGx) biomarkers and to evaluate whether there is a possible relationship to Vigantol® oil treatment outcomes.<br>;Primary end point(s): The primary endpoint is a composite endpoint of MRI and clinical variables:<br>• The primary MRI endpoint is the mean change from baseline in the total volume of T2 lesions at Week 48.<br>• The primary clinical endpoint is the proportion of relapse-free patients at Week 96.<br>
- Secondary Outcome Measures
Name Time Method