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

NCT01285401 | Completed Phase 2 Results DMC

• 2 other identifiers: EMR 200136-5322010-020328-23
• Study Type: interventional
• Target: 260
• Locations: 12 countries
• Sites: 38

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects With Disease Activity Free Status up to Week 48

  Disease activity free status was defined as absence of any of the clinical and imaging parameters related to the assessment of disease activity; no relapses, no expanded disability status scale (EDSS) progression and no new gadolinium (Gd)-enhancing or relaxation time 2 (T2) magnetic resonance imaging (MRI) lesions.

  Up to Week 48

Secondary Outcomes (15)

• Percentage of Relapse-free Subjects at Week 48

  Week 48

• Percentage of Subjects Free From Any Expanded Disability Status Scale (EDSS) Progression at Week 48

  Week 48

• Number od Subjects With Confirmed EDSS Progression

  Baseline upto 48 Weeks

• Cumulative Number of Relaxation Time 1 (T1) Gadolinium Enhancing Lesions at Week 48

  48 Weeks

• Mean Number of Combined Unique Active (CUA) Lesions Per Subject Per Scan at Week 48

  48 Weeks

Study Arms (3)

VigantOL® oil

EXPERIMENTAL

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

Drug: VigantOL oil plus interferon beta-1a (Rebif)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo plus interferon beta-1a (Rebif)

Rebif

EXPERIMENTAL

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

Biological: Interferon beta-1a (Rebif®) alone

Interventions

VigantOL oil plus interferon beta-1a (Rebif) 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.

VigantOL® oil

Placebo plus interferon beta-1a (Rebif) DRUG

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

Placebo

Interferon beta-1a (Rebif®) alone BIOLOGICAL

Rebif® 44 mcg tiw, sub-cutaneously alone.

Rebif

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (38)

Research Site

Vienna, Austria

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Esbjerg, Denmark

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Glostrup Municipality, Denmark

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Sønderborg, Denmark

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Vejle, Denmark

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Viborg, Denmark

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Tallinn, Estonia

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Helsinki, Finland

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Turku, Finland

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Bad Neustadt / Saale, Germany

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Bamberg, Germany

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Berlin, Germany

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Cologne, Germany

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Erlangen, Germany

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Freiburg im Breisgau, Germany

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Hanover, Germany

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Münster, Germany

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Regensburg, Germany

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Rostock, Germany

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Cefalù, Italy

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Riga, Latvia

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Kaunas, Lithuania

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Amsterdam, Netherlands

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Gouda, Netherlands

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Nieuwegein, Netherlands

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Rotterdam, Netherlands

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Sittard, Netherlands

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Bergen, Norway

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Lørenskog, Norway

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Tromsø, Norway

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Amadora, Portugal

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Lisbon, Portugal

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Porto, Portugal

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Bern, Switzerland

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Lausanne, Switzerland

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Lugano, Switzerland

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Sankt Gallen, Switzerland

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Zurich, Switzerland

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Related Publications (1)

• Hupperts R, Smolders J, Vieth R, Holmoy T, Marhardt K, Schluep M, Killestein J, Barkhof F, Beelke M, Grimaldi LME; SOLAR Study Group. Randomized trial of daily high-dose vitamin D3 in patients with RRMS receiving subcutaneous interferon beta-1a. Neurology. 2019 Nov 12;93(20):e1906-e1916. doi: 10.1212/WNL.0000000000008445. Epub 2019 Oct 8.

  PMID: 31594857 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Interferon beta-1a; Single Person

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Manolo Beelke, MD, PhD

  WCT Worldwide Clinical Trials GER GmbH Germany

  STUDY DIRECTOR

• Prof. Dr. Raymond Hupperts, MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2011
• First Posted: January 28, 2011
• Study Start: February 1, 2011
• Primary Completion: April 1, 2015
• Study Completion: May 1, 2015
• Last Updated: November 28, 2016
• Results First Posted: July 11, 2016

Record last verified: 2016-10

Locations

NL (5); LI (1); LA (1); CH (5); PT (3); AU (1); DK (5); NO (3); ES (1); IT (1); DE (10); FI (2)