A Comparative Clinical Effectiveness Trial of Rituximab Versus Ravulizumab, Inebilizumab, Satralizumab and Eculizumab To Prevent Relapses in Neuromyelitis Optica Spectrum Disorder
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 540
- 试验地点
- 6
- 主要终点
- Time to adjudicated relapse
研究概览
简要总结
Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare autoimmune condition that mainly affects the eyes and spinal cord, causing serious symptoms such as vision loss, paralysis, and severe pain. This trial compares the effectiveness and safety of five medications commonly used to prevent NMOSD relapses: rituximab, ravulizumab, inebilizumab, satralizumab, and eculizumab.
In this study, 160 adults with NMOSD who test positive for a specific antibody (AQP4-IgG) will participate. They will be randomly assigned to receive either rituximab or one of the four other FDA-approved medications. The main goal is to find out which treatment best prevents relapses and has fewer serious side effects. The trial will also measure disability, patient satisfaction, quality of life, and biomarkers that help track disease activity.
Participants will have regular assessments, including medical exams, surveys, and tests for vision, walking ability, and brain function. They will report any side effects or health issues experienced during the study. The trial will last from one to four years for each participant.
This research aims to help patients and doctors make better-informed treatment decisions by providing clear evidence about the best available therapies for NMOSD.
详细描述
Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune inflammatory disorder primarily affecting the optic nerves and spinal cord, leading to symptoms such as blindness, severe muscle weakness, paralysis, and significant pain. This study aims to directly compare the clinical effectiveness and safety profiles of five distinct therapies widely utilized to prevent disease relapses in patients with NMOSD who test positive for aquaporin-4 antibodies (AQP4-IgG): rituximab, ravulizumab, inebilizumab, satralizumab, and eculizumab.
The study is designed as an international, multicenter, randomized, adaptive clinical trial. It involves enrolling 160 adult participants diagnosed with AQP4-IgG positive NMOSD, who will be randomized in equal numbers to receive either rituximab or one of the four other FDA-approved therapies-ravulizumab, inebilizumab, satralizumab, or eculizumab. Patients randomized to the non-rituximab group will undergo further randomization into one of these four comparator medications. Additionally, the study incorporates an observational cohort for patients who decline randomization but agree to be followed according to the same protocol.
The primary objective is to evaluate the comparative effectiveness of rituximab versus the other treatments in preventing NMOSD relapses and treatment failure due to adverse events. Secondary objectives include comparing disability outcomes, evaluating treatment-related adverse events, and assessing impacts on patient-reported quality of life, as well as examining changes in biomarkers relevant to NMOSD disease activity.
Participants will undergo comprehensive evaluations at regular intervals, including detailed neurological examinations, standardized functional assessments (Expanded Disability Status Scale [EDSS], Multiple Sclerosis Functional Composite [MSFC]), visual acuity and contrast sensitivity testing, and cognitive assessments. Additionally, patient-reported outcomes such as fatigue, pain, mental health status, and overall quality of life will be collected systematically through validated surveys. Safety assessments will include regular monitoring of blood work, clinical evaluations for infections and other complications, and documentation of all adverse events.
Advanced exploratory analyses will also include biomarker studies involving optical coherence tomography (OCT) to assess retinal nerve fiber layer loss, and assays for serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels. The study will track direct and indirect healthcare costs, as well as impacts on employment and caregiver burden.
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
- Double (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
- •Diagnosis of NMOSD according to the 2015 International Panel for NMO Diagnosis (IPND) consensus criteria.
- •Seropositivity for AQP4 immunoglobulin G (AQP4-IgG) confirmed by a cell-based assay (either live or fixed) that meets the threshold for positivity set by the local testing laboratory.
- •Age ≥18 years at the time of consent.
- •Ability and willingness to provide informed consent and comply with all study procedures, including scheduled visits, laboratory tests, and assessments.
- •Eligible to receive any of the study drugs based on clinical judgment
排除标准
- •Known active hepatitis B virus (HBV) infection, defined as a positive hepatitis B surface antigen or detectable HBV DNA by PCR.
- •Known active hepatitis C virus (HCV) infection, defined as detectable HCV RNA by PCR.
- •Known active or latent tuberculosis, evidenced by a positive interferon-gamma release assay (IGRA) unless fully treated per local guidelines before enrollment.
- •Known or suspected immunodeficiency disorders, including but not limited to HIV infection with CD4 count <200 cells/mm³ or any condition requiring chronic immunosuppressive therapy outside the scope of the study drugs.
- •Pregnancy or breastfeeding, or intention to conceive during the study period. Pregnancy is excluded due to insufficient safety data for the investigational treatments in this population. Women of childbearing potential must agree to use effective contraception throughout the study and for a defined period following the last dose of study drug, per product labeling or institutional guidance.
- •Any medical, psychiatric, or neurological condition that, in the investigator's opinion, may interfere with study participation, pose additional risk to the participant, or confound interpretation of study results.
- •Inability or unwillingness to comply with the requirements of the protocol, including scheduled visits, evaluations, or procedures, based on investigator assessment.
- •Known hypersensitivity or severe allergic reaction to any component of the study drugs or pre-medications required for infusion.
研究组 & 干预措施
Open-label, non-randomized
Open-label, non-randomized
干预措施: Eculizumab (Soliris®) (Drug)
Open-label, non-randomized
Open-label, non-randomized
干预措施: Inebilizumab (Drug)
Inebilizumab
干预措施: Inebilizumab (Drug)
Complement inhibitors
Ravulizumab or eculizumab
干预措施: Ravulizumab (Drug)
Complement inhibitors
Ravulizumab or eculizumab
干预措施: Eculizumab (Soliris®) (Drug)
Rituximab
干预措施: Rituximab (R) (Drug)
Open-label, non-randomized
Open-label, non-randomized
干预措施: Satralizumab (Drug)
Satralizumab
干预措施: Satralizumab (Drug)
Open-label, non-randomized
Open-label, non-randomized
干预措施: Rituximab (R) (Drug)
Open-label, non-randomized
Open-label, non-randomized
干预措施: Ravulizumab (Drug)
结局指标
主要结局
Time to adjudicated relapse
时间窗: From date of randomization until the date of adjudicated relapse or first treatment discontinuation, whichever comes first, assessed up to 48 months
As determined by the blinded Relapse Adjudication Committee using pre-specified clinical and imaging criteria
Time to adjudicated safety or tolerability failure
时间窗: From date of randomization until the date of first adjudicated safety or tolerability failure or adjudicated relapse, whichever comes first, assessed up to 48 months
Includes adverse events, tolerability, patient preference, or logistical barriers.
次要结局
- Brief Pain Inventory(Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months)
- PROMIS Depression Short form(Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months)
- Expanded Disability Status Scale (EDSS)(Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months)
- Timed 25-Foot Walk(Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months)
- 9-Hole Peg Test(Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months)
- Symbol Digit Modalities Test (SDMT)(Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months)
- Landolt High Contrast Visual Acuity(Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months)
- Landolt Low Contrast Visual Acuity(Baseline and every 12 months through study completion, an average of 30 months and a maximum of 48 months)
- Treatment Satisfaction Questionnaire for Medication II (TSQM-II)(Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months)
- EuroQol 5-Dimension 5-Level (EQ-5D-5L)(Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months)
- Fatigue Scale for Motor and Cognitive Function(Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months)
- Visual Function Questionnaire 25(Baseline and every 6 months through study completion, an average of 30 months and a maximum of 48 months)
研究者
Philippe A. Bilodeau, MD
Principal investigator
Massachusetts General Hospital