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®
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 260
- 试验地点
- 1
- 主要终点
- Percentage of Subjects With Disease Activity Free Status up to Week 48
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
VigantOL® oil
VigantOL oil plus Rebif in subjects with 25-hydroxy-vitamin D plasma levels below 150 nmol/L
干预措施: VigantOL oil plus interferon beta-1a (Rebif) (Drug)
Placebo
Placebo daily plus Rebif in subjects with 25-hydroxy-vitamin D plasma levels below 150 nmol/L
干预措施: Placebo plus interferon beta-1a (Rebif) (Drug)
Rebif
Rebif alone in subjects with 25-hydroxy-vitamin D plasma levels equal or higher than 150 nmol/L
干预措施: Interferon beta-1a (Rebif®) alone (Biological)
结局指标
主要结局
Percentage of Subjects With Disease Activity Free Status up to Week 48
时间窗: 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.
次要结局
- Mean Number of Combined Unique Active (CUA) Lesions Per Subject Per Scan at Week 48(48 Weeks)
- Cumulative Number of New Combined Unique Active (CUA) Lesions at Week 48(48 Weeks)
- Percentage of Relapse-free Subjects at Week 48(Week 48)
- Percentage of Subjects Free From T1 Gadolinium Enhancing Lesions at Week 48(48 Weeks)
- 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)
- Percentage of New T1 Hypointense Lesions (Black Holes) at Week 48 Within the Subgroup of New or Enlarging Non-enhancing T2 Lesions(48 Weeks)
- Total Number of Reported Relapses at All Time Points up to 48 Weeks(48 weeks)
- Percentage of Subjects Free From Any Expanded Disability Status Scale (EDSS) Progression at Week 48(Week 48)
- Mean Change From Baseline in the Total Volume of T2 Lesions at Week 48 (T2 Burden of Disease)(Baseline, 48 Weeks)
- Percentage of Subjects Free From New T1 Hypointense Lesions (Black Holes) at Week 48(48 Weeks)
- Annualized Relapse Rate at Week 48(48 weeks)
- Mean Change From Baseline in the Total Volume of T1 Hypo Intense Lesions at Week 48(Baseline, 48 Weeks)
- Number of Subjects With Relapse(Baseline upto 48 weeks)
- Percentage of Subjects Treated With Glucocorticoids Due to Relapses(Baseline upto 48 weeks)