E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-Remitting Multiple Sclerosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of Vigantol® oil versus placebo as add-on therapy in subjects with Relapsing-Remitting Multiple Sclerosis receiving treatment with Rebif®. |
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E.2.2 | Secondary objectives of the trial |
• 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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 </= 4.0 at Screening. 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. |
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E.4 | Principal 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. 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. |
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E.5 End points |
E.5.1 | 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 patients at Week 96.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 53 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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For administrative and safety reporting purposes, the end of the trial will be defined as the date of the final clinical database lock after the last subject has completed the Week 96/Early Termination visit and the safety follow-up visit 4 weeks after, at Week 100. This provides for a single and conservative definition across all trial sites. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |