Efficacy and Safety of Ofatumumab in AQP4-IgG Seropositive NMOSD: an Open-label, Single-arm, Multicentre Prospective Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Change from baseline in annual relapse rate (ARR) at last follow-up visit
研究概览
简要总结
This is an open-label, single-arm, multicentre prospective pilot study to assess the efficacy and safety of ofatumumab in patients with AQP4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) in China.
详细描述
Neuromyelitis optica spectrum disorder (NMOSD) is a rare but severe demyelinating disorder that affects mainly adult patients. It is associated with a pathological B cell-mediated humoral immune response against the aquaporin-4 (AQP4) water channel. Monoclonal antibodies against CD20 have been shown to be effective for prevention of relapses in patients with NMOSD, and therefore been recommended as first-line therapy for this disorder. Ofatumumab (OFA), a fully humanized anti-CD20 monoclonal antibody, has been approved for multiple sclerosis treatment. However, prospective multicenter studies are needed to determine the efficacy and safety of ofatumumab in treating NMOSD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Diagnosis of NMOSD according to the 2015 International Panel Diagnostic Criteria for NMOSD with AQP4-IgG.
- •Clinical evidence of at least 2 relapses (including first attack) in past 24 months with at least 1 relapse occurring in the preceding 12 months.
- •Adults aged ≥18 years old.
- •Expanded disability status scale (EDSS) score between 0 and 7.5 (inclusive).
- •Provision of written informed consent to participate in this study.
- •Only oral corticosteroids were permitted at screening (≤10mg equivalent per day), which should be terminated within one month.
- •Effective contraception was used for female patients with fertility during the treatment or at least 3 months after stopping medication.
排除标准
- •Progressive neurological deterioration unrelated to relapses of NMOSD, or presence of neurological findings suspected with PML.
- •Pregnant or breastfeeding patients and those with family planning during the study period.
- •Patients participating in any other clinical therapeutic study at the screening or within 30 days of screening.
- •Patients with splenectomy or history of no spleen, and those with planned surgery (excluding minor surgery) during the study period.
- •Presence of uncontrolled severe concurrent diseases; long-term glucocorticoids or immunosuppressants use due to other autoimmune diseases, or presence of other chronic diseases that cannot receiving immunosuppression.
- •Active infection at within 4 weeks before baseline.
- •Positive for HBV or HCV.
- •Evidence of latent or active tuberculosis (TB).
- •Have received any live or live-attenuated vaccine within 6 weeks before baseline.
- •History of malignancy in past 5 years, including solid tumor, malignant hematopathy and carcinoma in situ.
- •History of severe allergic reactions to biological agents.
- •Inability to provide written informed consent.
研究组 & 干预措施
Ofatumumab
The enrolled patients will receive ofatumumab (20 mg/0.4 ml) subcutaneously administered at baseline, Day 7, Day 14 and monthly thereafter. Patients will receive ofatumumab therapy for a total of 48 weeks.
干预措施: Ofatumumab (Drug)
结局指标
主要结局
Change from baseline in annual relapse rate (ARR) at last follow-up visit
时间窗: baseline, 12 months
Pre-treatment ARR was determined at baseline by the total number of attacks divided by disease course from onset to baseline; post-treatment ARR is determined at 12 months after treatment by the number of relapses divided by 12 months.
次要结局
- Change from baseline in Expanded Disability Status Scale (EDSS) score(baseline, 3 months, 6 months, 9 months, 12 months)
- Change from baseline in lesion burden on MRI T2-weighted images(baseline, 6 months, 12 months)
- Change from baseline in immune landscape(baseline, 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months)
- Adverse events(1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months)
- Change from baseline in optic coherence tomography (OCT) measures(baseline, 6 months, 12 months)
- Change from baseline in the frequencies of circulating B cell subsets(baseline, 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months)
- Biochemical indicators monitoring(baseline, 1 month, 3 months, 6 months, 9 months, 12 months)
- Assessment of functional questionnaire(baseline, 1 month, 3 months, 6 months, 9 months, 12 months)
研究者
Jun Guo, MD
Department of Neurology
Tang-Du Hospital