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

NCT ID: NCT01285401

Last Updated: 2016-11-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2015-05-31

Brief Summary

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).

Conditions

Relapsing-Remitting Multiple Sclerosis

Keywords

Multiple Sclerosis; Rebif; VigantOL® oil; Vitamin D; Add-on treatment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

VigantOL® oil

VigantOL oil plus Rebif in subjects with 25-hydroxy-vitamin D plasma levels below 150 nmol/L

Group Type: EXPERIMENTAL

VigantOL oil plus interferon beta-1a (Rebif)

Intervention Type: DRUG

VigantOL oil 6,670 International Units per day (IU/d) (167 microgram per day \[mcg/day\]), was administered orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) administered orally for 44 weeks on top of Rebif 44mcg three times per week (tiw) administered subcutaneously.

Placebo

Placebo daily plus Rebif in subjects with 25-hydroxy-vitamin D plasma levels below 150 nmol/L

Group Type: PLACEBO_COMPARATOR

Placebo plus interferon beta-1a (Rebif)

Intervention Type: DRUG

Matching placebo daily, orally administered matched placebo for 48 weeks on top of Rebif 44 mcg tiw.

Rebif

Rebif alone in subjects with 25-hydroxy-vitamin D plasma levels equal or higher than 150 nmol/L

Group Type: EXPERIMENTAL

Interferon beta-1a (Rebif®) alone

Intervention Type: BIOLOGICAL

Rebif® 44 mcg tiw, sub-cutaneously alone.

Interventions

VigantOL oil plus interferon beta-1a (Rebif)

VigantOL oil 6,670 International Units per day (IU/d) (167 microgram per day \[mcg/day\]), was administered orally for 4 weeks followed by 14,007 IU/d (350 mcg/d) administered orally for 44 weeks on top of Rebif 44mcg three times per week (tiw) administered subcutaneously.

Intervention Type: DRUG

Placebo plus interferon beta-1a (Rebif)

Matching placebo daily, orally administered matched placebo for 48 weeks on top of Rebif 44 mcg tiw.

Intervention Type: DRUG

Interferon beta-1a (Rebif®) alone

Rebif® 44 mcg tiw, sub-cutaneously alone.

Intervention Type: BIOLOGICAL

Eligibility 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
• Expanded Disability Status Scale (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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manolo Beelke, MD, PhD

Role: STUDY_DIRECTOR

WCT Worldwide Clinical Trials GER GmbH Germany

Prof. Dr. Raymond Hupperts, MD

Role: PRINCIPAL_INVESTIGATOR

Dept of Neurology, Orbis Medical Center Sittard, Maastricht University, The Netherlands

Locations

Research Site

Vienna, , Austria

Research Site

Esbjerg, , Denmark

Research Site

Glostrup Municipality, , Denmark

Research Site

Sønderborg, , Denmark

Research Site

Vejle, , Denmark

Research Site

Viborg, , Denmark

Research Site

Tallinn, , Estonia

Research Site

Helsinki, , Finland

Research Site

Turku, , Finland

Research Site

Bad Neustadt / Saale, , Germany

Research Site

Bamberg, , Germany

Research Site

Berlin, , Germany

Research Site

Cologne, , Germany

Research Site

Erlangen, , Germany

Research Site

Freiburg im Breisgau, , Germany

Research Site

Hanover, , Germany

Research Site

Münster, , Germany

Research Site

Regensburg, , Germany

Research Site

Rostock, , Germany

Research Site

Cefalù, , Italy

Research Site

Riga, , Latvia

Research Site

Kaunas, , Lithuania

Research Site

Amsterdam, , Netherlands

Research Site

Gouda, , Netherlands

Research Site

Nieuwegein, , Netherlands

Research Site

Rotterdam, , Netherlands

Research Site

Sittard, , Netherlands

Research Site

Bergen, , Norway

Research Site

Lørenskog, , Norway

Research Site

Tromsø, , Norway

Research Site

Amadora, , Portugal

Research Site

Lisbon, , Portugal

Research Site

Porto, , Portugal

Research Site

Bern, , Switzerland

Research Site

Lausanne, , Switzerland

Research Site

Lugano, , Switzerland

Research Site

Sankt Gallen, , Switzerland

Research Site

Zurich, , Switzerland

Countries

Belgium; Hungary; Austria; Denmark; Estonia; Finland; Germany; Italy; Latvia; Lithuania; Netherlands; Norway; Portugal; Switzerland

Other Identifiers

2010-020328-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMR 200136-532

Identifier Type: -

Identifier Source: org_study_id