Relapsing-Remitting Multiple Sclerosis MedDRA version: 14.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Vigantol Oel
Product Name: Vigantol Oil
Product Code: 200106 or EMD 28162
Pharmaceutical Form: Oral solution
INN or Proposed INN: COLECALCIFEROL
CAS Number: 67-97-0
Current Sponsor code: 2
Sponsors
Merck Serono
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Diagnosis of a relapsing-remitting form of MS •Brain and/or spinal MRI with findings typical of MS •A first clinical event prior to Screening. •Disease activity •EDSS score of less than, or equal to 4.0 at Screening. •Currently treated with interferon-beta-1a 44µg (tiw) sc •Willingness and ability to comply with the protocol •Written informed consent 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 230 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Pregnancy and lactation period •Any disease other than MS that could better explain signs and symptoms. •Complete transverse myelitis or bilateral optic neuritis. •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. •Use of any cytokine (other than interferon) or anti-cytokine therapy, intravenous immunoglobulin, plasmapheresis, or any investigational drug or experimental procedure •Use of oral or systemic corticosteroids or ACTH •Have experienced a relapse within 30 days before the SD1 visit •Have abnormalities of Vitamin D related hormonal system other than low dietary intake or decreased sun exposure, i.e. primary hyperparathyroidism or granulomatous disorders. •Have an urine calcium/creatinine (mmol/mmol) ratio greater than 1.0 or hypercalcaemia •Are taking medications that influence Vitamin D metabolism other than corticosteroids, e.g., phenytoin, barbiturates, thiazide diuretics and cardiac glycosides. •Are taking more than 1000 IU (25 µg) of Vitamin D supplement daily. •Have conditions with increased susceptibility to hypercalcaemia, e.g., known arrhythmia or heart disease, treatment with Digitalis, or Hydrochlorothiazide and those who suffer from nephrolithiasis. •Have inadequate liver function •Moderate to severe renal impairment •Inadequate bone marrow reserve •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). •History or presence of severe depression, history of suicide attempt, or current suicidal ideation. •Epilepsy or seizures not adequately controlled by treatment. •Current or past alcohol or drug abuse. •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. •Known contra-indication to treatment with vitamin D •Known hypersensitivity to interferon or its excipient(s) •Known hypersensitivity to gadolinium. •Any other condition that would prevent the subject from undergoing an MRI scan. •Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such. •Positive HIV, hepatitis C, or hepatitis B (HBsAg and HBc antibody) serology (test performed at screening). •Legal incapacity or limited legal capacity. •Another current autoimmune disease, except diabetes.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 (Week48), • To explore pharmacogenetics (PGx), gene expression and circulating biomarkers and to evaluate whether there is a possible relationship to Vigantol® oil treatment outcomes.;Primary end point(s): • The proportion of subjects with DAF status at Week 48. DAF status is defined as a condition described by the absence of all of the following conditions: — Occurrence of relapse — EDSS progression — New MRI lesions: • Gd-enhancing • T2 lesions ;Timepoint(s) of evaluation of this end point: Proportion of Disease Activity Free subjects at week 48;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
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Proportion of relapse-free subjects at week 48 •Proportion of subjects free from any EDSS progression at week 48 •Time to confirmed EDSS progression •Proportion of subjects free from confirmed EDSS progression at week 48 •Mean number of new T1 gadolinium-enhancing lesions per subject per scan at week 48 •Cumulative number of T1 gadolinium enhancing lesions at Week 48 •Cumulative number of new CUA lesions at week 48 •Mean number of CUA lesions per subject per scan at week 48 •Mean change from baseline in the total volume of T2 lesions at week 48 (T2 Burden of disease) [mm³] •Proportion of subjects free from new T1-hypointense lesions (black holes) at week 48 •Change in cognitive function at weeks 24 and 48 with respect to baseline as measured by Symbol Digit Modalities Test •Proportion of T1 gadolinium-enhancing lesions at Study Day 1 (SD1) that transform into black holes at week 48 •Percent Brain Volume Change (PBVC) at week 48 with respect to baseline, and at week 96 with respect to week 48 •Change from baseline in MSFC composite score at Weeks 12, 24, 36, 48 •Time to first documented relapse •Annualized relapse rate at Weeks 48 •Total number of reported relapses at all time points •Proportion of subjects treated with glucocorticoids due to relapses (during 48 weeks) •Proportion of subjects free from T1 gadolinium enhancing lesions at Week 48 •Percentage of new T1-hypointense lesions (black holes) at Weeks 48 within the subgroup of new or enlarging non-enhancing T2 lesions •Mean change from baseline in total volume of T1 hypointense lesions at Week 48 (in mm³);Timepoint(s) of evaluation of this end point: As described in Section E.5.2 | — |
Countries
Austria, Belgium, Denmark, Estonia, Finland, Germany, Italy, Latvia, Lithuania, Netherlands, Norway, Portugal, Switzerland
Contacts
Public ContactCommunication Center Merck KGaA
Merck Serono
Outcome results
None listed