NCT02228213已完成2 期
A Phase 2B Randomised, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of MIS416 in the Treatment of Subjects With Secondary Progressive Multiple Sclerosis
Innate Immunotherapeutics7 个研究点 分布在 2 个国家目标入组 93 人开始时间: 2014年10月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 93
- 试验地点
- 7
- 主要终点
- Change from baseline of neuromuscular function at 12 months
研究概览
简要总结
The purpose of this study is to determine whether MIS416 administered once weekly over 12 months is safe, tolerable, and improves a range of signs and symptoms associated with secondary progressive multiple sclerosis.
详细描述
The primary objectives of the study are to:
- Determine the efficacy of MIS416, relative to placebo, when administered repeatedly via weekly intravenous (IV) administration to subjects with Secondary Progressive Multiple Sclerosis, as assessed by its effect on measures of neuromuscular function.
- Determine the safety and tolerability of a weekly regimen of MIS416.
The secondary objectives of the study are to:
- Determine the effect of MIS416 on disease activity and neurodegeneration by assessing changes in Magnetic Resonance Imaging (MRI) markers including lesions, whole brain atrophy (WBA) and Magnetization Transfer Ratio (MTR).
- Determine the effect of MIS416 on Patient Reported Outcomes (PRO) related to disability and health status.
- Assess, in a subset of subjects, the pharmacodynamic (PD) effects of MIS416, including effects on serum, Peripheral Blood Mononuclear Cell (PBMC), and Cerebral Spinal Fluid (CSF) cytokine/chemokine levels and expression patterns.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A historical or current cranial MRI scan demonstrating T2-hyperintense lesions consistent with MS.
- •Has SPMS as determined by the 2010 Update to the McDonald Criteria
- •An Expanded Disability Status Scale (EDSS) of 3.0 to 6.5 at Screening.
- •Has SPMS which, in the judgment of the investigator, has been clinically active and functionally progressive within the 2 years prior to Screening
- •The absence of MS relapse for at least two years prior to Baseline.
- •Neurologically stable for at least four weeks prior to Screening.
- •Has the following laboratory values within three days prior to initiation of Investigational Product:
- •Absolute neutrophil count (ANC) >= 1 x 109/L;
- •Platelet count >= 100 x 109/L;
- •Serum creatinine =< 1.5 mg/dL;
- •Aspartate aminotransferase (AST) =<2 × upper limit of normal;
- •Alanine aminotransferase (ALT) =< 2 × upper limit of normal.
- •Provided written informed consent to participate.
排除标准
- •Has primary Progressive MS (PPMS), Relapsing Remitting (RRMS), or progressive relapsing MS as determined by the 2010 update to the McDonald Criteria.
- •Has not completed the discontinuation period for approved and/or investigational multiple sclerosis disease modifying therapies prior to screening.
- •Has had any other immunomodulatory drug therapy or immunosuppressive therapy within four weeks prior to Screening, or systemic corticosteroids within the eight weeks prior to Screening.
- •Any previous exposure to investigational MS therapeutic vaccines.
- •Any use of cell-depleting monoclonal antibodies including, but not limited to, Rituximab, or Ocrelizumab.
- •A diagnosis or history of collagen vascular disease (including Sjögren's syndrome and systemic lupus erythematosus), anticardiolipin antibody syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, sarcoidosis, vasculitis, Behcet's syndrome and/or Lyme disease.
- •Contraindication to MRI (e.g., pacemaker or other contraindicated implanted metal device, allergy to gadolinium, or unmanageable claustrophobia).
- •A history of alcohol or drug abuse (including cannabinoid use) within two years prior to Screening.
- •Has had major surgery or radiation therapy within four weeks prior to Screening.
- •Has an active infection requiring antibiotics within two weeks prior to Screening.
- •Has had active malignancy within two years of Screening, with the exception of basal cell carcinoma and squamous cell carcinoma of the skin.
- •Uncontrolled congestive heart failure, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, or transient ischemic attack within twelve weeks prior to Screening.
- •Has angina, other symptomatic coronary artery disease, or known cardiomyopathy.
- •Has symptomatic cardiac dysrhythmias requiring treatment, or persistent prolongation of the QTcF (Fredericia) interval to > 450 msec for males or > 470 msec for females.
研究组 & 干预措施
Treatment
Experimental
500 mcg MIS416 500 at 0.2 mg/mL administered i.v. once weekly for 52 weeks
干预措施: MIS416 (Biological)
Saline
Placebo Comparator
Saline administered i.v. once weekly for 52 weeks
干预措施: Saline (Drug)
结局指标
主要结局
Change from baseline of neuromuscular function at 12 months
时间窗: Baseline, 3, 6, 9 and 12 months
Neuromuscular function will be assessed using the following test: * MS Function Composite (MSFC), comprising the; timed 25 Foot Walk, 9 Hole Peg Test (9HPT), and Paced Auditory Serial Addition Test (PASAT); * Jebsen Hand Function Test (JHFT); * Grip, tip and key pinch strength; * Symbol digit modalities test (SDMT); * Sloan low-contrast letter visual acuity (SLCVA); * 6-minute walk test (6MWT);
Proportion of Participants with Serious and Non-Serious Adverse Events
时间窗: Up to 12 months
Safety assessments will be conducted at each study visit and include; characterization of the type, incidence, severity, timing, seriousness, and relationship to treatment of adverse events (AEs); effects on vital signs and clinical laboratory parameters; changes on electrocardiograms (ECGs); and at 3 months and 12 months - the number of gadolinium-enhancing lesions on cranial MRI assessments.
次要结局
- Change from baseline of activity of immune biomarkers in cerebrospinal fluid (CSF)(Up to 12 months)
- Change from baseline of neurodegeneration by assessing changes in Magnetic Resonance Imaging (MRI) markers at 12 months(Baseline, 3, and 12 months)
- Change from baseline of disability and health status at 12 months(Baseline, 3, 6, 9, and 12 months)
- Change from baseline of activity of immune biomarkers in serum(Up to 1 year)
- Change from baseline in Peripheral Blood Mononuclear Cell (PBMC) immune biomarkers(Up to 12 months)
研究者
研究点 (7)
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