Eculizumab Add-On Therapy in the Acute Phase of Neuromyelitis Optica Spectrum Disorder: A Multicenter Prospective Real-World Study
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Expanded Disability Status Scale score,EQ-5D-5L,
研究概览
简要总结
This project is a multi-center, prospective, real-world cohort study that collects clinical data of Chinese patients with AQP4-positive NMOSD in the acute stage. It comprehensively assesses the clinical outcomes of the patients and aims to compare the clinical efficacy and safety of icoxib as a combined add-on treatment versus simple hormone shock therapy during the acute phase of NMOSD.Using simple hormone shock therapy (IVMP) as the control group, the efficacy and safety of etanercept treatment in the acute attack phase of Chinese patients with AQP4-positive neuromyelitis optica spectrum disorder (NMOSD) were evaluated.
详细描述
Patients who met the inclusion and exclusion criteria were divided into three groups for their acute-phase treatment based on their treatment preferences:
- Eculizumab plus treatment group: Eculizumab + IVMP (intravenous methylprednisolone pulse therapy)
- Human immunoglobulin addition treatment group: IVIG + IVMP
- Single IVMP treatment group: IVMP
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18 - 65 years old, gender not restricted.
- •Patients who meet the diagnostic criteria for NMOSD as set by the International Panel for NMO Diagnosis (IPND) in 2015, and have positive serum AQP4-IgG (by CBA method or live cell method).
- •Acute phase of NMOSD-ON, defined as new or worsening optic nerve dysfunction (visual acuity decline accompanied or not by eye pain and visual field defect), with an onset duration of ≤ 21 days, and clear evidence of new or recurrent optic nerve damage on imaging (new or expanded T2WI lesions, with enhancement); the best corrected visual acuity (BCVA) of the affected eye during the acute phase of NMOSD-ON (if both eyes are affected simultaneously, the worse eye is considered) drops from above 0.3 to ≤ 0.
- •Acute phase of NMOSD-TM, defined as new or worsening spinal cord dysfunction (limb weakness or numbness, accompanied or not by urinary and defecation disorders), with an onset duration of ≤ 21 days, and clear evidence of new or recurrent spinal cord damage on imaging (new or expanded T2WI lesions, with enhancement); the EDSS score during the acute phase of NMOSD-TM increases from ≤ 4.0 to ≥ 6.
- •Clinical onset and recurrence determination requires unanimous judgment by each center and the center committee (an independent group of 3 people).
- •Agree to receive meningococcal vaccine or use eculizumab during and 2 weeks after the medication.
- •Sign the informed consent.
排除标准
- •Damage to the optic nerve or spinal cord caused by other non-NMOSD-related factors.
- •Abnormal laboratory indicators that need to be excluded from the subjects include, but are not limited to the following indicators:
- •Neutrophils < 1.5 × 109/L, Hemoglobin < 90g/L, Platelet count < 75 × 109/L; Serum creatinine > 1.5 × ULN, Total bilirubin > 1.5 × ULN, Aspartate aminotransferase (AST) > 1.5 × ULN, Alanine aminotransferase (ALT) > 1.5 × ULN, Alkaline phosphatase > 2 × ULN ； HbA1c > 8% (for diabetic patients); GFR < 60 mL/minute/1.73m
- •Pregnant or lactating women, as well as those planning to become pregnant during the study period.
- •Those who have received PE/IA/IVIG/FcRn/B-cell deletion/C5/IL-6 treatment within 1 month before enrollment.
- •Active infections: active hepatitis B, hepatitis C, syphilis or HIV infection; active systemic infections or immunodeficiency diseases; unrelieved meningococcal infection of the meninges, or patients with severe infections that cannot use immunosuppressive drugs.
- •Patients with severe internal or external diseases (not limited to such as heart failure, unstable angina pectoris, respiratory failure, pulmonary insufficiency, cachexia, organ transplantation, etc.).
- •Those who have had or currently have an untreated malignant tumor that is not well controlled.
- •Patients with serious physical or mental diseases that may affect the smooth implementation of the study.
- •Patients known to be allergic to monoclonal drugs, murine proteins or any excipients.
- •Patients who are intolerant to methylprednisolone or gamma globulin.
- •Patients who cannot complete the magnetic resonance enhanced scan screening.
- •Patients who are participating in other interventional clinical trials.
- •Patients who cannot understand the questionnaire questions or cooperate with the questionnaire survey.
- •Situations that the research team collectively deems unsuitable for participation in this study.
研究组 & 干预措施
Eculizumab+IVMP
Eculizumab add-on treatment group: 1) The timing of eculizumab addition treatment should be within the 1000mg hormone treatment window; 2) Intravenous infusion of 900mg once a week for a total of 4 weeks; 3) The hormone administration regimen is the same as that of the hormone monotherapy group. All patients receiving eculizumab treatment are required to use prophylactic antibiotics and/or vaccination.
干预措施: Eculizumab+IVMP (Drug)
IVIG+IVMP
Gamma globulin treatment group: 1) The administration of gamma globulin should occur within the 1000mg hormone treatment window; 2) The infusion dose is 0.4g/kg·d * 5; 3) The hormone administration regimen is the same as that of the single hormone treatment group.
干预措施: IVIG+IVMP (Drug)
IVMP
Single hormone shock therapy group: 1) Initiate hormone shock therapy during the acute phase of the attack (≤ 21 days); 2) Intravenous injection of methylprednisolone (IVMP) for 14 days: 1000 mg/day (5 days), 500 mg (3 days), 240 mg (3 days), 120 mg (3 days), then switch to oral administration.
干预措施: IVMP (Drug)
结局指标
主要结局
Expanded Disability Status Scale score,EQ-5D-5L,
时间窗: baseline (before the acute attack and before the initiation of this treatment), and after hormone treatment at weeks 1, 2, 3, 4, 8 and 12
Evaluate the EDSS score, EQ-5D-5L,
Expanded Disability Status Scale
时间窗: Baseline (before the acute attack treatment), after 1st, 2nd, 3rd, 4th week of hormone treatment, 8th and 12th week
The EDSS score is evaluated by neurologists through a systematic examination. It is based on the assessment of the central nervous system functions (FS). Lower scores focus on evaluating functional impairments, such as numbness in the face or fingers, and visual disorders. Higher scores focus on evaluating functional impairments of the motor system, mainly difficulty in walking. The symptoms are scored from normal (0 points) to severe disability (5-6 points) across 8 systems (pyramidal tract function, cerebellar function, brainstem system function, sensory system function, bladder and rectal function, visual function, mental system function, and mobility function). The EDSS score mainly assesses the patient's neurological functional impairments and the severity of the disease. The score range is 0 to 10 points. The higher the score, the more severe the neurological functional impairment. A score of 0 indicates a normal healthy state, and a score of 10 indicates the death of MS.
次要结局
未报告次要终点
研究者
Zhang Li
Associate Chief Physician of Neuroimmunology Subspecialty
Chinese PLA General Hospital