A Multi-center, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Daratumumab in Patients With Anti-Aquaporin 4 Antibody Positive Neuromyelitis Optica Spectrum Disorders (NMOSD)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 135
- 试验地点
- 1
- 主要终点
- Participants With An Adjudicated On-trial Relapse
研究概览
简要总结
The objectives of this time-to-event study are to assess the efficacy and safety of Daratumumab as compared with placebo in participants with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody-positive. NMOSD is an autoimmune disease of the central nervous system that predominantly affects the spinal cord, optic nerves, and area postrema. It is usually mediated by the pathogenic AQP4-IgG. Antibody-secreting cells (ASCs) have been recognized as essential sources of AQP4-IgG. CD38 is a glycoprotein that is highly expressed on ASCs. Daratumumab, a CD38-directed monoclonal antibody, has been shown to decrease the levels of autoantibodies in lupus, myasthenia gravis, or autoimmune encephalitis. This randomized controlled study aims to evaluate the therapeutic potential of daratumumab in NMOSD.
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
- Quadruple (Participant, Care Provider, Investigator, 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
- •Male or female participants ≥ 18 years old.
- •Diagnosis of NMO or NMOSD.
- •Anti-AQP4 antibody seropositive.
- •Historical relapse of at least 1 relapses in the last 12 months or 2 relapses in the last 24 months with at least 1 relapse in the 12 months prior to the screening.
- •Expanded Disability Status Scale score ≤ 7.
- •Patients must give written informed consent.
排除标准
- •Use of intravenous steroid pulse therapy or intravenous immunoglobulin or plasma exchange/adsorption within 3 weeks prior to Screening.
- •Use of tocilizumab, satralizumab, belimumab, ofatumumab within 1 months prior to Screening.
- •Patients treated with oral immunosuppressive agents other than steroids (e.g. azathioprine, mycophenolate mofetil, methotrexate, tacrolimus, cyclosporine in the 3 months prior to allocation.
- •Use of rituximab or inebilizumab within 6 months prior to Screening.
- •Patients infected with hepatitis B or C virus, or human immunodeficiency virus, or those having active infectious diseases.
- •Patients with a severe chronic infection or a history of recurrent infections.
- •Patients with a history of radiation treatment (whole body irradiation or lymphoid irradiation) or stem cell transplantation.
- •Patients who are pregnant or breast-feeding.
- •Patients who are participating in other clinical trials for NMOSD.
- •Patients diagnosed with cancer.
研究组 & 干预措施
Daratumumab
Induction Period: Participants received daratumumab (8mg/kg) via intravenous (IV) every 2 weeks for two cycles. This was followed by the Maintenance Period: Participants received daratumumab (4mg/kg) via IV infusion every 4 weeks from the third dose (Week 4) onwards.
干预措施: Daratumumab (Drug)
Placebo
Placebo contains the same buffer components without the active ingredient. Induction Period: Participants received matching placebo (8mg/kg) via intravenous (IV) every 2 weeks for two cycles. This was followed by the Maintenance Period: Participants received matching placebo (4mg/kg) via IV infusion every 4 weeks from the third dose (Week 4) onwards.
干预措施: Placebo (Drug)
结局指标
主要结局
Participants With An Adjudicated On-trial Relapse
时间窗: Baseline, Up To 52 Weeks (End of Study)
An On-trial Relapse was defined as a new onset of neurologic symptoms or worsening of existing neurologic symptoms with an objective change (clinical sign) on neurologic examination that persisted for more than 24 hours as confirmed by the treating physician. An adjudicated On-trial Relapse was defined by the protocol and positively adjudicated by the relapse adjudication committee.
次要结局
- Percentage of Blood Neurofilament Light Chain (NFL) Over Time(Baseline, Weeks 2, 4, 8, 12, 24, 48)
- Change From Baseline In Hauser Ambulation Index (HAI) Score At End of Study(Baseline, Up To 52 Weeks (End of Study))
- Number of Participants With Adverse Events Serious Adverse Events (SAEs)(Baseline, Up To 52 Weeks (End of Study))
- Change From Baseline in Best Corrected Binocular Visual Acuity to the end of study(Baseline, Up To 52 Weeks (End of Study))
- Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the end of study(Baseline, Up To 52 Weeks (End of Study))
- Percentage of Blood Antibody-Secreting Cells (ASCs) Over Time(Baseline, Weeks 2, 4, 8, 12, 24, 48)
- Adjudicated On-trial Annualized Relapse Rate (ARR)(Baseline, Up To 52 Weeks (End of Study))
- Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the end of study(Baseline, Up To 52 Weeks (End of Study))
- Blood AQP4-IgG Concentration Over Time(Baseline, Weeks 2, 4, 8, 12, 24, 48)
- Percentage of Blood Glial Fibrillary Acidic Protein (GFAP) Over Time(Baseline, Weeks 2, 4, 8, 12, 24, 48)
- Change From Baseline In Modified Rankin Scale (mRS) Score At End Of Study(Baseline, Up To 52 Weeks (End of Study))
- Change From Baseline In European Quality Of Life (EuroQoL) Health 5-Dimension Questionnaire (EQ-5D) Visual Analogue Scale At End Of Study(Baseline, Up To 52 Weeks (End of Study))
- Change From Baseline In EuroQoL EQ-5D Index Score At End Of Study(Baseline, Up To 52 Weeks (End of Study))
- Change From Baseline in Speed of Timed 25-Foot Walk (T25W) at 24 Week Intervals During the DB Period(Baseline, Up To 52 Weeks (End of Study))
- Number of Participants With Adverse Events (AEs)(Baseline, Up To 52 Weeks (End of Study))
研究者
Fu-Dong Shi
Professor
Tianjin Medical University General Hospital