Eculizumab For Acute Attack of Neuromyelitis Optica Spectrum Disorder (NMOSD): a Multi-Center, Phase 2 Trial (EASE-NMO)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Proportion of improvement in OSIS from baseline to Day 28 by 2 points or more
研究概览
简要总结
Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, inflammatory autoimmune disorder of the central nervous system characterized by the pathogenic anti-aquaporin 4 antibody (AQP4-IgG). The objectives of this study are to assess the efficacy and safety of eculizumab for treatment of patients with neuromyelitis optica spectrum disorders during acute phase who are anti-aquaporin-4 (AQP4) antibody-positive. Eculizumab, a humanized monoclonal antibody, inhibits the terminal complement protein C5 and prevents its cleavage into C5a and the formation of C5b-9 (MAC), has approved for preventive treatment of NMOSD. Given the high efficacy of C5 inhibition, eculizumab is proposed to potentially provide rapid relief from astrocyte destruction by reducing MAC formation, which could contribute to the fast alleviation of neurological deficit during NMO acute attack. The potential of eculizumab warrants further investigation as a treatment for acute neuromyelitis optica spectrum disorders attacks.
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
- Single (Outcomes Assessor)
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
- •Anti-AQP4 antibody seropositive.
- •Male or female patients ≥18 years old
- •Body weight ≥ 35 kg
- •Acute optic neuritis and/or transverse myelitis enrolled within 28 days from the attack, with a change in neurological exam that meet an increase of OSIS at least 2 points of baseline compared to that of prior attack.
- •A female subject is eligible to enter the trial if she is:
- •Not pregnant or breastfeeding, not intending to conceive during the course of the trial
排除标准
- •Use of IVIg within 3 weeks prior to screening
- •Unresolved meningococcal infection
- •Any systemic bacterial or other infection which is clinically significant in the opinion of the Investigator and has not been treated with appropriate antibiotics
- •Participation in any other investigational drug study or was exposed to an investigational drug or device within 30 days of screening.
- •Has previously received treatment with eculizumab
- •Hypersensitivity to murine proteins or to one of the excipients of eculizumab
- •Any medical condition that, in the opinion of the Investigator, might interfere with thepatient's participation in the trial, poses any added risk for the patient, or confounds the assessment of the patients
研究组 & 干预措施
Intravenous Methylprednisolone (IVMP) arm
IVMP arm: 1000mg methylprednisolone x5d, oral prednisone 60mg, 5mg weekly decline + antibiotics
干预措施: Intravenous Methylprednisolone (IVMP) (Drug)
IVMP+Eculizumab arm
IVMP+Eculizumab arm: eculizumab (900 mg) will be administered intravenously once per week for a total of four doses (days 1, 8, 15, and 22) in conjunction with IVMP and oral prednisone (60mg, 5mg weekly decline).
All enrolled patients will receive antibiotic prophylaxis against N meningitidis.
干预措施: Intravenous Methylprednisolone (IVMP) (Drug)
IVMP+Eculizumab arm
IVMP+Eculizumab arm: eculizumab (900 mg) will be administered intravenously once per week for a total of four doses (days 1, 8, 15, and 22) in conjunction with IVMP and oral prednisone (60mg, 5mg weekly decline).
All enrolled patients will receive antibiotic prophylaxis against N meningitidis.
干预措施: Complement protein C5 inhibitor (Drug)
结局指标
主要结局
Proportion of improvement in OSIS from baseline to Day 28 by 2 points or more
时间窗: Acute attack to Day 28
The Optic-Spinal Impairment Score (OSIS) was developed to measure the disability status of subjects with demyelinating disease. It allows an objective quantification of the level of functioning that could be widely and reproducibly used by researchers and health care providers. OSIS score ranges from 0 to 25, which includes four primary functions: Visual Acuity (VA) (0-8), Motor Function (0-7), Sensory Function (0-5), and Sphincter Function (0-5). The higher scores reflect more severe disability. A decrease of at least 2 points in the overall OSIS score on day 28 compared to the baseline was regarded as a significant improvement.
次要结局
- Change of OSIS from baseline to Day 28(Acute attack to Day 28)
- Change of EDSS from baseline to Day 28(Acute attack to Day 28)
- Proportion of subjects that require plasma exchange or immunoadsorption at day 10 post treatment initiation.(Acute attack to Day 10)
- Change of OSIS from baseline to Day 7, 14, 21, and Week 12.(Acute attack to Week 12)
- Change of EDSS from baseline to Day 7, 14, 21, and Week 12(Acute attack to Week 12)
- Changes in Muscle Strength by MRC Scale for patients presenting with an acute relapse of myelitis at Days 7, 14, 21,28 and Week 12.(Acute attack to Week 12)
- Changes in visual acuity in subjects presenting with an acute relapse of optic neuritis at Days 7, 14, 21,28, and Week 12(Acute attack to Week 12)
- Changes of pRNFL measured by OCT in subjects presenting with an acute relapse of optic neuritis at Days 28, and Week 12(Acute attack to Week 12)
- Changes of mGCIPLT measured by OCT in subjects presenting with an acute relapse of optic neuritis at Day 28, and Week 12(Acute attack to Week 12)
- To evaluate the changes of Nfl from baseline to Day 28(Acute attack to Day 28)
- To evaluate the changes of GFAP from baseline to Day 28(Acute attack to Day 28)
- To evaluate the changes of complement activity (CH50) from baseline to Day 28(Acute attack to Day 28)
- To compare the change in MRI lesion size by T2 weighted imaging and T1 post-contrast imaging from baseline to Week 12(Acute attack to Week 12)
研究者
Fu-Dong Shi
Professor
Tianjin Medical University General Hospital