FcRn Antagonists (Efgartigimod) for Acute Neuromyelitis Optica Spectrum Disorders (NMOSD) Attack: a Phase 2, Randomized Controlled Trial.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 63
- 主要终点
- Change in Neurological Disability - Expanded Disability Scale Score
研究概览
简要总结
NMOSD is an autoimmune disease of the central nervous system that predominantly affects the spinal cord and optic nerves. The objectives of this study are to assess the efficacy and safety of FcRn antagonists (efgartigmod) for treatment of patients with neuromyelitis optica spectrum disorders during acute phase who are anti-aquaporin-4 (AQP4) antibody-positive. The potential of efgartigimod, an IgG1 Fc fragment that competes with IgG for FcRn binding, thereby lowering IgG levels, warrants further investigation as a treatment for acute neuromyelitis optica spectrum disorders attacks. This study aims to evaluate the therapeutic potential of efgartigmod in acute NMOSD attack.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, ages 18 to
- •Meet the 2015 International Panel of Experts (IPND) diagnostic criteria for neuromyelitis optica spectrum disorders.
- •Acute EDSS nadir of 2.5-7.5, and a change of at least 0.5 points from baseline due to an acute relapse event.
- •Confirmation of serum AQP4-IgG antibody positivity using the CBA assay.
- •Confirmation of an acute attack of neuromyelitis optica spectrum disorders either with an acute optic neuritis and/or acute myelitis, defined as a worsening in the patient's signs and symptoms of neurological/visual impairment, an increase in the EDSS score, and symptoms lasting more than 24 hours and occurring more than 1 month since the last attack. Combination of imaging and clinical evaluation will be used to assess relapse and rule out a pseudorelapse.
- •New lesions or enhanced lesions need to be found in MRI.
- •Subjects who were receiving immunosuppressive therapy prior to the screening period will be required to agree to discontinue immunosuppression.
- •Treatment is stable at least 3 months.
排除标准
- •Other core clinical symptoms besides optic neuritis and myelitis.
- •Severe neuromyelitis optica spectrum disorder attack, which in the judgment of the investigator is not appropriate for this study. Severe is defined as requiring assisted ventilation or likely to require assisted ventilation during the study based on the judgment of the investigator.
- •Subjects with total IgG levels ≤ 6 g/L at screening.
- •Subjects with a B-cell count ≤ 5% of the lower limit of normal at screening.
- •Received high-dose intravenous methylprednisolone within 4 weeks prior to the screening period.
- •Received intravenous immunoglobulin, plasma exchange, or immunoadsorption treatment within 4 weeks prior to the screening period.
- •Received a vaccination within the first 4 weeks of the screening period or planned during the study.
- •Using of a monoclonal antibody or investigational drug not mentioned above that has immunomodulatory effects within 3 months or 5 half-lives (whichever is longer) prior to the screening period.
- •Subject is known to be allergic to any component of the study drug or any other FcRn drug or contrast medium for enhanced MRI.
- •Subject is known to have contraindications to taking methylprednisolone (for subjects in A and B group).
- •Subjects with clinically significant active infections (including unresolved or inadequately treated infections, including active tuberculosis) as assessed by the investigator.
- •Subjects with positive screening tests for hepatitis B and C who have received live or live attenuated vaccine within 6 weeks prior to baseline.
- •Subjects is known unable to taken MRI.
- •Subjects is known to have other ophthalmic disease that affect vision as assessed by the investigator.
研究组 & 干预措施
Efgartigimod+IVMP group
Patients will receive efgartigimod alpha via intravenous infusion at a dose of 10 mg/kg, each infusion lasting approximately 2 hours, on Week 0, 1, 2 and 3. Efgartigimod should be administered no later than the second day after initiation of high-dose intravenous methylprednisolone therapy. This is delivered intravenously at a dosage of 1,000 mg/day for five consecutive days, which is then reduced to 500 mg/day for the next three days, followed by 240 mg/day for another three days, and then 120 mg/day for an additional three days. Subsequently, the treatment shifts to oral prednisone, starting with 60 mg daily for seven days, then decreasing to 50 mg daily for the next seven days, followed by 40 mg daily for another seven days. Afterward, the prednisone dosage is reduced by 5 mg every two weeks until it reaches 10 mg. After Week 4, Inebilizumab to prevent relapse will be introduced according to the indication.
干预措施: Efgartigimod Alfa Injection (Drug)
Efgartigimod+IVMP group
Patients will receive efgartigimod alpha via intravenous infusion at a dose of 10 mg/kg, each infusion lasting approximately 2 hours, on Week 0, 1, 2 and 3. Efgartigimod should be administered no later than the second day after initiation of high-dose intravenous methylprednisolone therapy. This is delivered intravenously at a dosage of 1,000 mg/day for five consecutive days, which is then reduced to 500 mg/day for the next three days, followed by 240 mg/day for another three days, and then 120 mg/day for an additional three days. Subsequently, the treatment shifts to oral prednisone, starting with 60 mg daily for seven days, then decreasing to 50 mg daily for the next seven days, followed by 40 mg daily for another seven days. Afterward, the prednisone dosage is reduced by 5 mg every two weeks until it reaches 10 mg. After Week 4, Inebilizumab to prevent relapse will be introduced according to the indication.
干预措施: High-dose intravenous methylprednisolone (Drug)
IVMP group
Patients will be treated with injectable methylprednisolone sodium succinate as described in Arm A. After Week 4, Inebilizumab to prevent relapse will be introduced according to the indication.
干预措施: High-dose intravenous methylprednisolone (Drug)
Efgartigimod group
Patients will be treated with efgartigimod alpha injection via intravenous infusion at a dosage of 10 mg/kg, with each session lasting approximately 2 hours, on Week 0, 1, 2 and 3. After Week 4, Inebilizumab to prevent relapse will be introduced according to the indication.
干预措施: Efgartigimod Alfa Injection (Drug)
结局指标
主要结局
Change in Neurological Disability - Expanded Disability Scale Score
时间窗: Acute nadir to week4
The Kurtzke Expanded Disability Status Scale (EDSS) 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. The EDSS provides a total score on a scale that ranges from 0 to 10 where 0 is normal and 10 is deceased. Increasing disability is reflected in an increasing EDSS score.
次要结局
- The vital signs, clinical laboratory indices, and electrocardiogram records of the subjects during the study period.(Baseline to Week 24.)
- The proportion of participants requiring rescue treatment during the study period.(Baseline to Week 24.)
- The incidence of adverse events in the subjects during the study period.(Baseline to Week 24.)
- Change of high-contrast visual acuity in subjects with acute optic neuritis.(Baseline to Week 4, 12 and 24.)
- Change of OCT measurements in subjects with acute optic neuritis.(Baseline to Week 4, 12 and 24.)
- Change of EDSS score, FS score, and MRC score at Week 4 and 24.(Baseline to Week 4 and Week 24.)
- Change of EQ-5D-5L score.(Baseline to Week 4, 12 and 24.)
- Change of FS score and MRC score at Week 12.(Baseline to week 12.)
研究者
Fu-Dong Shi
Professor
Beijing Tiantan Hospital