A Multicentre, Randomised, Double-blind, Placebo-controlled Study of the Efficacy of Supplementary Treatment With Cholecalciferol (Vitamin D3) in Patients With Relapsing- Multiple Sclerosis (RMS) Treated With Subcutaneous Interferon Beta-1a 44 µg 3 Times Weekly
Overview
- Phase
- Phase 2
- Intervention
- Cholecalciferol (Vitamin D3)
- Conditions
- Multiple Sclerosis
- Sponsor
- Merck KGaA, Darmstadt, Germany
- Enrollment
- 129
- Locations
- 1
- Primary Endpoint
- Annualized Relapse Rate
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The aim of this multicentre, randomised, double-blind, placebo-controlled study is to evaluate the efficacy and safety of supplementary treatment with cholecalciferol (vitamin D3) in subjects with relapsing multiple sclerosis (R MS) treated with subcutaneous (s.c.) interferon beta-1a 44 microgram (mcg) [Rebif] 3 times weekly. The subjects will be divided into 2 groups, one receiving cholecalciferol 100,000 IU twice monthly along with Rebif treatment and the other group will be on placebo along with Rebif treatment. A total of 200 subjects will be recruited in 20-30 centres in France.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of RRMS according to Poser criteria (clinically definite multiple sclerosis \[CDMS\] or laboratory supported definite multiple sclerosis \[LSDMS\]) or according to McDonald criteria (2005).
- •Subjects aged between 18 and 65 years.
- •Treated with interferon beta-1a 44 mcg (or 22 mcg in case of intolerance to 44 mcg) 3 times weekly subcutaneously for 4 months ± (2 months) at the randomization visit (V1).
- •Expanded disability status scale (EDSS) score between 0 and
- •At least one documented episode during the last two year.
- •Stable disease with no episodes over the last 30 days.
- •Serum 25-hydroxyvitamin D less than (\<) 75 nanomolar per liter (nmol/l) at randomization visit.
- •Women must not be pregnant or breast-feeding, and women of childbearing age must meet the following criteria:
- •Surgically sterilised, or
- •Using a highly effective contraceptive method throughout the entire duration of the study. A highly effective contraceptive method is defined as a method with a very low failure rate (i.e. \< 1 % per year) with regular and appropriate use, e.g. implants, injectable contraceptives, combined oral contraceptives, coil, abstinence or vasectomised partner.
Exclusion Criteria
- •Hormonal abnormalities associated with vitamin D other than low dietary intake or reduced exposure to sun, for example malabsorption (coeliac disease, Whipple's disease, inflammatory bowel disease, intestinal derivation, short bowel syndrome), cirrhosis, nephrotic syndrome, hyperthyroidism, rickets, hypoparathyroidism, cancer, granulomatous diseases (sarcoidosis, silicosis) and lymphomas known at the initial visit.
- •Patients with osteoporosis or known osteopenia.
- •Use of medicines affecting vitamin D metabolism other than corticosteroids, e.g. anticonvulsants (phenobarbital, primidone, phenytoin), rifampicin, isoniazid, ketoconazole, 5-FU and leucovorin, or thiazide diuretics.
- •Previous or ongoing hypercalcaemia.
- •Situations involving increased susceptibility to hypercalcaemia, e.g. known cardiac arrhythmia or cardiac disease, treatment with digitalis, renal lithiasis.
- •Any contraindication to the treatment (cholecalciferol) stated in the summary of product characteristics.
- •Moderate renal impairment defined as creatinine clearance between 30 and 60 ml/min.
- •An active episode during the month prior to inclusion in the study.
- •Inadequate liver function, defined as total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase greater than (\>) 2.5 \* upper limit of normal.
- •Severe renal impairment defined as creatinine clearance below 30 milliliter per minute (ml/min).
Arms & Interventions
Cholecalciferol
Subjects receive Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 3 times a week.
Intervention: Cholecalciferol (Vitamin D3)
Cholecalciferol
Subjects receive Cholecalciferol 100,000 IU one dose fortnightly (equivalent to a daily dose of approximately 7142 IU) for 96 weeks treatment period along with subcutaneous Rebif 3 times a week.
Intervention: Rebif
Placebo
Subjects receive matching placebo to Cholecalciferol once every two weeks along with subcutaneous injection of Rebif 3 times weekly.
Intervention: Placebo
Placebo
Subjects receive matching placebo to Cholecalciferol once every two weeks along with subcutaneous injection of Rebif 3 times weekly.
Intervention: Rebif
Outcomes
Primary Outcomes
Annualized Relapse Rate
Time Frame: 2 years post treatment (IMP) administration
The annualized relapse rate was calculated for each treatment group as follows: the number of relapses observed during the study period divided by the time spent in the study (in years).
Secondary Outcomes
- Time to First Documented Relapse(2 years post treatment (IMP) administration)
- Mean Number of Relapses Per Subject(2 years post treatment (IMP) administration)
- Number of Relapse-Free (Documented) Subjects(2 years post treatment (IMP) administration)
- Cumulative Probability of Progression of Disability (Kaplan-Meier Curves)(Baseline up to week 96)
- Number of New or Extended Lesions by T1- and T2-Weighted Magnetic Resonance Imaging (MRI)(2 years post treatment (IMP) administration)
- Changes From Baseline in Measured Lesion Load (T2)(Baseline, Week 96)
- Change From Baseline in Measurement and Evaluation of Cognitive Ability by Paced Auditory Serial Addition Task (PASAT) Total Score At Week 96(Baseline, Week 96)
- Change From Baseline in Euro Quality of Life Scale (EuroQol) 5-Dimension-3 Level (EQ-5D-3L)(2 years post treatment (IMP) administration)
- Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Abnormal Clinical Laboratory(Baseline up to end of treatment (week 96))