Safety and Efficacy of Tocilizumab Versus Azathioprine in Neuromyelitis Optica Spectrum Disorders: a Randomized, Controlled, Open-label, Phase 2 Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 118
- 试验地点
- 1
- 主要终点
- Time to first relapse
研究概览
简要总结
In neuromyelitis optica spectrum disorder (NMOSD),interleukin-6 (IL-6) may play an important role in facilitating plasma cells to produce pathological aquaporin 4 (AQP4) autoantibody. Inhibition of IL-6 signaling pathway by Tocilizumab (ACTEMRA®), a humanized monoclonal antibody may have shown beneficial clinical effects in a few patients with NMOSD.
Larger scale clincial trials may be needed to observe its efficacy and safety. Here, by choosing azathioprine, one of the most frequently used medication in case of relapses, the investigators compare the safety and efficacy of tocilizumab in preventing NMOSD attacks.
详细描述
The investigators primarily aim to observe the time to first relapse from initiation of tocilizumab or azathioprine treatment. The proportion of participants who experience relapse-free in one year follow-up will be compared.
The secondary outcomes are to determine: The safety profile of tocilizumab and azathioprine in participants with NMO and whether tocilizumab improves visual function, Expanded Disability Status Scale (EDSS), et al.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients ≥ 18 years old
- •Diagnosis of NMO or NMO spectrum disorder
- •Clinical evidence of at least 2 relapses in last 12 months or 3 relapses in the last 24 months
- •Able and willing to give written informed consent and comply with the requirements of the study protocol.
- •EDSS <= 7.5 (8 in special circumstances)
- •Men and women of reproductive potential must agree to use a highly effective method of birth control from screening to 6 months after final dose of the investigational product.
排除标准
- •Current evidence or known history of clinically significant infection (Herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus,human immunodeficiency virus, Hepatitis viruses, Syphilis, etc)
- •Pregnant, breastfeeding, or child-bearing potential during the course of the study
- •Patients will not participate in any other clinical therapeutic study or will not have participated in any other experimental treatment study within 30 days of screening
- •Participation in another interventional trial within the last 3 months
- •Heart or kidney insufficiency
- •Tumor disease currently or within last 5 years
- •Clinically relevant liver, kidney or bone marrow function disorder
- •Intolerance of azathioprine or previous relapses on azathioprine treatment
- •Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal.
研究组 & 干预措施
Tocilizumab
Tocilizumab Injection (ACTEMRA®) , a IL-6 receptor blockade
干预措施: Tocilizumab Injection (Drug)
Azathioprine
Imuran
干预措施: Azathioprine (Drug)
结局指标
主要结局
Time to first relapse
时间窗: From baseline to one year after
An acute attack was defined as a new neurological worsening lasting for at least 24 hours and occurring more than 30 days after the previous attack.
次要结局
- Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 24 Weeks(From baseline to 60 weeks)
- Change in Low-contrast Letter Acuity (LCLA) at Week 60(From baseline to 60 weeks)
- Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI)(From baseline to 60 weeks)
- Determination of serum cytokines(From baseline to 60 weeks)
- Worsening in EDSS(Worsening from baseline in EDSS to 60 weeks)
- Proportion of patients who experience relapse-free(From baseline to 60 weeks)
- Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks(From baseline to 60 weeks)
- Change in High-contrast Letter Acuity (HCLA) at Week 60(From baseline to 60 weeks)
- Determination of serum immunoglobulins(From baseline to 60 weeks)
- Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks(From baseline to 60 weeks)
- Counts of peripheral blood B cell subsets(From baseline to 60 weeks)
- Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks(From baseline to 60 weeks)
- Percentage change in SD-OCT Average Retinal Ganglion Cell Layer/Inner Plexiform Retinal Layer (RGCL/IPL) at Week 60(From baseline to 60 weeks)
- Overall safety and tolerability of tocilizumab or azathioprine(From baseline to 60 weeks)
- Percentage Change in Spectral-domain Optical Coherence Tomography (SD-OCT) Average Retinal Nerve Fiber Layer (RNFL) Thickness at Week 60(From baseline to 60 weeks)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(From baseline to 60 weeks)
- Determination of serum AQP4 antibodies(From baseline to 60 weeks)
研究者
Fu-Dong Shi
Director of Neurology Department
Tianjin Medical University General Hospital