A Phase II Randomized, Double-Blind, Parallel-Group, Placebo Controlled Crossover Trial to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Clemastine Fumarate as a Remyelinating Agent in Multiple Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Full Field Visual Evoked Potential (VEP)
研究概览
简要总结
The main purpose of this study is to assess clemastine as a remyelinating agent in patients with relapsing forms of multiple sclerosis. The study will also evaluate the tolerability of clemastine, originally approved as first-generation antihistamine, in patients with multiple sclerosis. Study procedures will include assessments for evidence of remyelination in the anterior visual pathway and in the brain using electrophysiologic techniques and magnetic resonance imaging. The study will also assess the robustness and stability of this clinical effect in patients taking clemastine for up to 3 months. Patients in this study can remain on their standard disease modifying treatment during the course of the study. However, patients cannot participate in any other investigational new drug research study concurrently.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsing remitting Multiple Sclerosis by 2010 Revised McDonald Criteria
- •Latency delay > 125 milliseconds on baseline full-field transient pattern reversal visual evoked potential (VEP) in at least one eye (electrophysiological evidence of demyelination)
- •Retinal nerve fiber layer (RNFL) > 70 microns on Spectralis Domain Optical Coherence Topography (SD-OCT) in the same eye meeting criteria for latency delay (sufficient axons)
- •No optic neuritis in prior 6 months
- •Stable immunomodulatory therapy - no switch or planned switch in > 6 months and no change in doses in 30 days prior to screening
- •Use of appropriate contraception during period of trial (females of child bearing potential)
- •Understand and sign informed consent.
- •Expanded disability status scale (EDSS) 0-6.0 (inclusive)
排除标准
- •Major ophthalmologic disease / Concomitant ophthalmologic disorders (e.g. diabetes, macular degeneration, glaucoma, severe myopia , etc).
- •Myopia > -7 Diopters (Severe myopia)
- •History of significant cardiac conduction block
- •History of cancer
- •Known optic neuritis in involved eye > 5 years ago OR disease duration > 15 years
- •Suicidal ideation or behaviour in 6 months prior to screening
- •Pregnancy, breastfeeding, or planning to become pregnant.
- •Involved with other study protocol simultaneously without prior approval.
- •Concomitant use of Dalfampridine (4AP or diamino4AP) or any other formulation of 4AP or diamino4AP.
- •Concomitant use of any other putative remyelinating therapy as determined by investigator.
- •Treatment with corticosteroids within 30 days prior to screening
- •Prior treatment with total lymphoid irradiation, T cell or T cell receptor vaccination
- •Prior treatment with alemtuzumab, mitoxantrone, or cyclophosphamide
- •Serum creatinine > 1.5 mg/dL; aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase > 2 times the upper limit of normal
- •History of drug or alcohol abuse within the past year
- •Untreated vitamin B12 deficiency (as determined by B12 serological assessments and metabolites including methylmalonic acid (MMA) and homocysteine) or untreated hypothyroidism
- •Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, psychiatric allergic, renal or other major diseases that in the PI's judgment may affect interpretation of study results or patient safety.
- •History of or presence of clinically significant medical illness or laboratory abnormality that, in the opinion of the investigator would preclude participation in the study
研究组 & 干预措施
3 months Clemastine, 2 months Placebo
4mg clemastine twice daily for first 3 months -- crossover -- equivalent quantity/frequency of placebo for last 2 months
干预措施: Clemastine (Drug)
3 months Clemastine, 2 months Placebo
4mg clemastine twice daily for first 3 months -- crossover -- equivalent quantity/frequency of placebo for last 2 months
干预措施: Placebo (Drug)
3 months Placebo , 2 months Clemastine
Placebo for first 3 months -- crossover -- 4mg clemastine twice daily for last 2 months.
干预措施: Clemastine (Drug)
3 months Placebo , 2 months Clemastine
Placebo for first 3 months -- crossover -- 4mg clemastine twice daily for last 2 months.
干预措施: Placebo (Drug)
结局指标
主要结局
Full Field Visual Evoked Potential (VEP)
时间窗: Treatment start to treatment end, up to 3 months.
The primary objective is to evaluate the efficacy of Clemastine relative to placebo for reducing P100 latencies on full field transient pattern reversal visual evoked potentials.Visual evoked potentials (VEP) are used primarily to measure the functional integrity of the visual pathways from the retina to the visual cortex of the brain. VEP latencies were collected at Baseline, Month 1, Month 3, and Month 5.
次要结局
- Tolerability of Clemastine in Multiple Sclerosis (MS) Patients(Treatment start to treatment end, up to 3 months.)
- Myelin Water Fraction (MWF) and Magnetization Transfer Ratios (MTR)(Treatment start to treatment end, up to 3 months.)
- Expanded Disability Status Scale (EDSS) Score(Start of treatment to end of treatment, up to 3 months)