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® SOLAR Supplementation of VigantOL® Oil versus Placebo as Add-on in Patients with Relapsing-Remitting MS receiving Rebif® treatment. - SOLAR

• Register: EUCTR
• Last refreshed on: 19 October 2015
• Main ID: EUCTR2010-020328-23-BE
• Date of registration: 18/11/2010
• Prospective Registration: Yes
• Primary sponsor: Merck Serono SA-Geneva an affiliate of Merck KgaA, Darmstadt
• Public title: 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® SOLAR Supplementation of VigantOL® Oil versus Placebo as Add-on in Patients with Relapsing-Remitting MS receiving Rebif® treatment. - SOLAR
• Scientific title: 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® SOLAR Supplementation of VigantOL® Oil versus Placebo as Add-on in Patients with Relapsing-Remitting MS receiving Rebif® treatment. - SOLAR
• Date of first enrolment: 01/04/2011
• Target sample size: 358
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020328-23
• 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

Countries of recruitment

Austria, Belgium, Denmark, Estonia, Finland, Germany, Italy, Latvia, Lithuania, Netherlands, Portugal

Key inclusion & exclusion criteria

Inclusion criteria:
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

Exclusion criteria:
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 Are taking more than 400IU (10micrograms) of Vitamin D supplement daily.
12. 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.
13. 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
14. 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])
15. Inadequate bone marrow reserve, defined by a WBC count < 0.5 times the lower limit of normal.
16. 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).
17. History or presence of severe depression, history of suicide attempt, or current suicidal ideation.
18. Epilepsy or seizures not adequately controlled by treatment.
19. Current or past (within the last 2 years) alcohol or drug abuse.
20. 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.
21. Known contra-indication to treatment with vitamin D (according to SPC)
22. Known hypersensitivity to IFN or its excipient(s) (according to SPC).
23. Known hypersensitivity to gadolinium.
24. Any other condition that would prevent the subject from undergoing an MRI scan.
25. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.
26. Positive HIV, hepatitis C, or hepatitis B (HBsAg and HBc antibody) serology (test performed at screening).
27. Legal incapacity or limited legal capacity.
28. Another current autoimmune disease

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

Health Condition(s) or Problem(s) studied

Relapsing-Remitting Multiple Sclerosis
MedDRA version: 12.1 Level: LLT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis

Intervention(s)

Trade Name: Vigantol Oel
Product Name: Vigantol Oil
Product Code: EMD 28162
Pharmaceutical Form: Oral solution
INN or Proposed INN: CHOLECALCIFEROL
CAS Number: 67-97-0
Current Sponsor code: EMD 28162, 300910
Other descriptive name: Cholecalciferol, Vitamin D3
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint is a composite endpoint of MRI and clinical variables:
• The primary MRI endpoint is the mean change from baseline in the total volume of T2 lesions at Week 48.
• The primary clinical endpoint is the proportion of relapse-free subjects at Week 96.

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.
• To assess changes in MRI parameters.
• To investigate the safety profile up to the end of the Treatment Period (Week 96),
• To explore pharmacogenetics/pharmacogenomics (PGx) biomarkers and to evaluate whether there is a possible relationship to Vigantol® oil treatment outcomes.

Secondary ID(s)

2010-020328-23-FI

EMR 200136-532