Supplementation of VigantOL® Oil Versus Placebo as Add-on in Patients With Relapsing Remitting Multiple Sclerosis Receiving Rebif® Treatment (SOLAR)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01285401
First received: January 26, 2011
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

The drug being tested is called VigantOL® oil - a very effective form of Vitamin D hormone supplement (cholecalciferol). Low levels of Vitamin D have been described to be associated with a higher risk of developing Multiple Sclerosis (MS), and it is known that up to 90% of patients with Multiple Sclerosis have Vitamin D deficiency.

Rebif® is known to be an effective treatment for slowing down the progression of MS. The purpose of this research trial is to evaluate if VigantOL® oil on top of Rebif® has any benefit on the progression of MS compared to Rebif® and placebo.

Disease activity will be assessed by clinical examination and Magnetic Resonance Imaging (MRI). The planned study treatment duration for each study participant is 48 weeks, and the study consists of a total of 8 visits. Study participants who are already passed Week 48 at the time of approval of Protocol Amendment 5 will have a study duration of 96 weeks and a total of 12 visits.

During the study, the participant will undergo physical examination, neurological assessments, safety assessments, blood tests and urinalysis (including pregnancy tests).


Condition Intervention Phase
Relapsing-Remitting Multiple Sclerosis
Drug: VigantOL® oil plus interferon beta-1a (Rebif®)
Drug: Placebo plus interferon beta-1a (Rebif®)
Biological: Interferon beta-1a (Rebif®) alone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official 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 44mg Tiw of Rebif®

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Percentage of subjects with disease activity free status (no relapses, no EDSS progression and no new Gd-enhancing or T2 MRI lesions) at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of relapse-free subjects at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Percentage of subjects free from any Expanded Disability Status Scale (EDSS) progression at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Time to confirmed EDSS progression [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Percentage of subjects free from confirmed EDSS progression at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Cumulative number of T1 gadolinium enhancing lesions at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Mean number of combined unique active (CUA) lesions per subject per scan at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Cumulative number of new combined unique active (CUA) lesions at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Mean change from baseline in the total volume of T2 lesions at Week 48 (T2 Burden of disease) [ Time Frame: Baseline and 48 Weeks ] [ Designated as safety issue: No ]
    Total volume of T2 lesions will be assessed in mm^3

  • Percentage of subjects free from T1 gadolinium enhancing lesions at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Percentage of subjects free from new T1 hypointense lesions (black holes) at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Percentage of new T1 hypointense lesions (black holes) at Week 48 within the subgroup of new or enlarging non-enhancing T2 lesions [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Time to first documented relapse [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Annualised relapse rate at Week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Total number of reported relapses at all time points up to 48 weeks [ Time Frame: up to 48 weeks ] [ Designated as safety issue: No ]
  • Percentage of subjects treated with glucocorticoids due to relapses [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Mean change from baseline in the total volume of T1 hypointense lesions at Week 48 [ Time Frame: Baseline and 48 Weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 230
Study Start Date: March 2011
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VigantOL® oil
VigantOL® oil plus Rebif® in subjects with 25-hydroxy-vitamin D plasma levels below 150 nmol/L (174 subjects)
Drug: VigantOL® oil plus interferon beta-1a (Rebif®)
VigantOL® oil 6,670 International Units/day (IU/d) (167 microgram per day [mcg/day]), orally administered for 4 weeks followed by 14,007 IU/d (350 mcg/d) orally administered for 44 weeks on top of Rebif® 44mcg three times per week (tiw) administered sub-cutaneously. Subjects who have already passed Week 48 at the time of approval of Protocol Amendment 5 in their country will be receive 14,007 IU/d (350 mcg/d) orally administered for 92 weeks.
Placebo Comparator: Placebo
Placebo daily plus Rebif® in subjects with 25-hydroxy-vitamin D plasma levels below 150 nmol/L (174 subjects)
Drug: Placebo plus interferon beta-1a (Rebif®)
Matching placebo daily, orally administered plus Rebif® 44 mcg tiw, sub-cutaneously.
Experimental: Rebif®
Rebif® alone in subjects with 25-hydroxy-vitamin D plasma levels equal or higher than 150 nmol/L
Biological: Interferon beta-1a (Rebif®) alone
Rebif® 44 mcg tiw, sub-cutaneously alone.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 44mg (tiw) sc
  • Willingness and ability to comply with the protocol
  • Written informed consent

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 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.
  • Have experienced a relapse within 30 days.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01285401

  Show 38 Study Locations
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Manolo Beelke, MD, PhD WCT Worldwide Clinical Trials GER GmbH Germany
Principal Investigator: Prof. Dr. Raymond Hupperts, MD Dept of Neurology, Orbis Medical Center Sittard, Maastricht University, The Netherlands
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01285401     History of Changes
Other Study ID Numbers: EMR 200136-532, 2010-020328-23
Study First Received: January 26, 2011
Last Updated: February 21, 2014
Health Authority: Austria: Agency for Health and Food Safety
Belgium: Ministry of Social Affairs, Public Health and the Environment
Denmark: Danish Medicines Agency
Estonia: The State Agency of Medicine
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Norway: Norwegian Medicines Agency
Switzerland: Swissmedic

Keywords provided by Merck KGaA:
Multiple Sclerosis
Rebif
VigantOL® oil
Vitamin D
Add-on treatment

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Interferon-beta
Interferons
Interferon beta 1a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on July 22, 2014