Clinical trial NCT01285401: Supplementation of VigantOL® Oil Versus Placebo as Add-on in Patients With Relapsing Remitting Multiple Sclerosis Receiving Rebif® 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®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsing-Remitting Multiple Sclerosis
Keywords: Multiple Sclerosis
Rebif
VigantOL® oil
Vitamin D
Add-on treatment
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2011-01-28
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Percentage of Subjects With Disease Activity Free Status up to Week 48
timeFrame: Up to Week 48
Secondary outcomes:
measure: Percentage of Relapse-free Subjects at Week 48
timeFrame: Week 48
measure: Percentage of Subjects Free From Any Expanded Disability Status Scale (EDSS) Progression at Week 48
timeFrame: Week 48
measure: Number od Subjects With Confirmed EDSS Progression
timeFrame: Baseline upto 48 Weeks
measure: Cumulative Number of Relaxation Time 1 (T1) Gadolinium Enhancing Lesions at Week 48
timeFrame: 48 Weeks
measure: Mean Number of Combined Unique Active (CUA) Lesions Per Subject Per Scan at Week 48
timeFrame: 48 Weeks
measure: Cumulative Number of New Combined Unique Active (CUA) Lesions at Week 48
timeFrame: 48 Weeks
measure: Mean Change From Baseline in the Total Volume of T2 Lesions at Week 48 (T2 Burden of Disease)
timeFrame: Baseline, 48 Weeks
measure: Percentage of Subjects Free From T1 Gadolinium Enhancing Lesions at Week 48
timeFrame: 48 Weeks
measure: Percentage of Subjects Free From New T1 Hypointense Lesions (Black Holes) at Week 48
timeFrame: 48 Weeks
measure: Percentage of New T1 Hypointense Lesions (Black Holes) at Week 48 Within the Subgroup of New or Enlarging Non-enhancing T2 Lesions
timeFrame: 48 Weeks
measure: Number of Subjects With Relapse
timeFrame: Baseline upto 48 weeks
measure: Annualized Relapse Rate at Week 48
timeFrame: 48 weeks
measure: Total Number of Reported Relapses at All Time Points up to 48 Weeks
timeFrame: 48 weeks
measure: Percentage of Subjects Treated With Glucocorticoids Due to Relapses
timeFrame: Baseline upto 48 weeks
measure: Mean Change From Baseline in the Total Volume of T1 Hypo Intense Lesions at Week 48
timeFrame: Baseline, 48 Weeks
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Research Site
city: Esbjerg
country: Denmark
facility: Research Site
city: Glostrup
country: Denmark
facility: Research Site
city: Sønderborg
country: Denmark
facility: Research Site
city: Vejle
country: Denmark
facility: Research Site
city: Viborg
country: Denmark
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
city: Helsinki
country: Finland
facility: Research Site
city: Turku
country: Finland
facility: Research Site
city: Bad Neustadt / Saale
country: Germany
facility: Research Site
city: Bamberg
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Münster
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Rostock
country: Germany
facility: Research Site
city: Cefalu
country: Italy
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Kaunas
country: Lithuania
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Gouda
country: Netherlands
facility: Research Site
city: Nieuwegein
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Sittard
country: Netherlands
facility: Research Site
city: Bergen
country: Norway
facility: Research Site
city: Lørenskog
country: Norway
facility: Research Site
city: Tromsø
country: Norway
facility: Research Site
city: Amadora
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Bern
country: Switzerland
facility: Research Site
city: Lausanne
country: Switzerland
facility: Research Site
city: Lugano
country: Switzerland
facility: Research Site
city: St. Gallen
country: Switzerland
facility: Research Site
city: Zurich
country: Switzerland
facility: Research Site
Study officials:
affiliation: WCT Worldwide Clinical Trials GER GmbH Germany
name: Manolo Beelke, MD, PhD
role: STUDY_DIRECTOR
affiliation: Dept of Neurology, Orbis Medical Center Sittard, Maastricht University, The Netherlands
name: Prof. Dr. Raymond Hupperts, MD
role: PRINCIPAL_INVESTIGATOR
References: