Natalizumab Temporary Discontinuation Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 4
- 主要终点
- Number gadolinium-enhancing lesions
研究概览
简要总结
This study evaluates the discontinuation of natalizumab either immediately or tapered off in the treatment of multiple sclerosis. Half of the fifty (50) participants will discontinue natalizumab immediately and the other half will taper off the drug, having two additional infusions, one at six weeks- and one at eight weeks-post discontinuation.
详细描述
Natalizumab is a pharmaceutical intervention used in the management of multiple sclerosis.
The decision to discontinue natalizumab therapy is often raised in patients defined as high-risk for PML despite good clinical efficacy. During the therapy cessation period following large phase III trials, a return to the prestudy disease activity was reached by four months post-discontinuation. Shorter therapy was associated with a trend for a more severe disease activity pointing to a possible 'rebound' effect after natalizumab discontinuation.
This study focuses on two different approaches: an immediate versus a step-wise/tapered down natalizumab discontinuation protocol, both with reinstitution of a different disease modifying therapy (DMT) within 1-6 months from the last natalizumab infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with relapsing-remitting or relapsing-progressive (relapsing-remitting with incomplete recovery and secondary progressive with superimposed relapses) MS according to the McDonald criteria who have been on natalizumab therapy for at least 12 months
- •Age 18-65
- •Have EDSS scores less than or equal to 7.0
- •Positive John Cunningham (JC) virus antibody results at screening
- •Signed informed consent
- •None of the exclusion criteria
排除标准
- •Patients not willing or able to personally provide informed consent (subjects with cognitive impairment that effects the ability to provide informed consent for participation)
- •Patients with active disease per clinical and MRI evaluation at baseline
- •Patients with renal disease that precludes having an MRI with gadolinium contrast
结局指标
主要结局
Number gadolinium-enhancing lesions
时间窗: Change between baseline-6 months, 6 months-12 months, and baseline-12 months
Number of gadolinium-enhancing lesions
Number of recorded infections including viral opportunistic infection
时间窗: Up to 1 year follow-up
Number of recorded infections including viral opportunistic infections (i.e., shingles) will be recorded up to 1-year follow-up; continuous close vigilance will be maintained for possible cases of progressive multifocal leukoencephalopathy (PML)
Absolute changes in gadolinium-enhancing and T2-weighted lesion volume between timepoints
时间窗: Change between baseline-6 months, 6 months-12 months, and baseline-12 months
Absolute changes in gadolinium-enhancing and T2-weighted lesion volume
Saturation percentage of α4β1integrin receptors on the surface of lymphocytes
时间窗: 12 months
Sum of new and enlarging T2-weighted lesions
时间窗: Change between baseline-6 months, 6 months-12 months, and baseline-12 months
Sum of new and enlarging lesions as seen on T2-weighted images
次要结局
- Number of clinical relapses(Either baseline (immediate discontinuation group) or 6 months (taper-off group))
- Expanded Disability Status Scale (EDSS) score(Either baseline (immediate discontinuation group) or 6 months (taper-off group))
研究者
Robert Zivadinov, MD, PhD
BNAC Director
University at Buffalo