A Randomized, Controlled, Multicenter Study To Evaluate the Safety and Efficacy of Tocilizumab In Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 102
- 试验地点
- 36
- 主要终点
- Time from randomization to the first MOGAD relapse as determined by an adjudication committee
研究概览
简要总结
The purpose of the study is to evaluate the safety and efficacy of Tocilizumab in MOGAD.
详细描述
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune disease of the central nervous system, which can cause optic neuritis, myelitis, brainstem encephalitis, or encephalitis. The specific autoantibody against myelin oligodendrocyte glycoprotein antibody (MOG-IgG) has been indicated to contribute to the pathogenesis of the disease. Data from several cohorts suggests that around 50% of adult patients with MOG-IgG may relapse within the first two years of the disease, with most of relapses occurring early after disease onset. Few randomized controlled trials have ever been performed and therapeutic guidelines for this disease remain unclear especially after a single event. There is no drug approved for MOGAD by FDA. IL-6 is a pro-inflammatory cytokine which can promotes B cell activation, blood-brain barrier dysfunction, leukocyte migration, and the production of autoantibodies. Tocilizumab (ACTEMRA®), a humanized monoclonal antibody against the IL-6 receptor, has shown beneficial clinical effects and reduction of the risk of relapses in some patients with MOGAD. However, the efficacy of tocilizumab in MOGAD warrants further clinical trials.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who are aged ≥12 years at the time of signing Informed Consent Form
- •Confirmed diagnosis of MOGAD with a history of ≥1 MOGAD relapse in the 12 months prior to screening or ≥2 attacks in the 24 months prior to screening
- •Anti-MOG antibody seropositive
- •For women of childbearing potential: participants who agree to remain abstinent or use adequate contraception during the treatment period and for at least 3 months after the final dose of tocilizumab
- •Patients must give written informed consent
排除标准
- •Any concomitant disease other than MOGAD that may require treatment with oral immunosuppressants or prednisone at doses >20 mg/day (or equivalent)
- •Receipt of the following at any time prior to randomization Alemtuzumab Total lymphoid irradiation Bone marrow transplant T-cell vaccination therapy Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal.
- •Receipt of intravenous immunoglobulin (IVIG) or plasma exchange (PE) within 1 month prior to randomization.
- •Receipt of any of the following within 3 months prior to randomization:
- •Natalizumab (Tysabri®). Methotrexate Mitoxantrone Cyclophosphamide Eculizumab
- •Receipt of any of the following within 6 weeks prior to randomization:
- •Tacrolimus Cyclosporin Mycophenolate mofetil
- •Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of tocilizumab
- •Participants with active or presence of recurrent bacterial, viral, fungal, mycobacterial infection, or other infection at baseline
- •Participants with evidence of latent or active tuberculosis (excluding patients receiving chemoprophylaxis for latent tuberculosis infection)
- •Participants with positive screening tests for hepatitis B and C
- •Receipt of live or live attenuated vaccine within 6 weeks prior to baseline
- •Known history of a severe allergy or reaction to any biologic therapy.
- •History of alcohol, drug, or chemical abuse, or a recent history of such abuse < 1 year prior to randomization
- •WBC < 3.0 × 10^3/mL, ANC < 2.0 × 10^3/mL, PLT < 10 × 10^4/mL, AST or ALT>1.5 ×ULN, Lymphocyte count < 0.5 × 10^3/mL
研究组 & 干预措施
Tocilizumab with oral prednisone
Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, with oral prednisone
干预措施: Tocilizumab (Drug)
Tocilizumab with oral prednisone
Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, with oral prednisone
干预措施: Prednisone (Drug)
Prednisone
干预措施: Prednisone (Drug)
结局指标
主要结局
Time from randomization to the first MOGAD relapse as determined by an adjudication committee
时间窗: Baseline, Up To 60 Weeks (End of Study)
An adjudicated relapse was defined by the protocol and positively adjudicated by the relapse adjudication committee.
次要结局
- Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the end of study(Baseline, Up To 60 Weeks (End of Study))
- Dosage of oral steroid at the end of the TOMATO trial(Baseline, Up To 60 Weeks (End of Study))
- Number of Participants With Adverse Events (AEs)(Baseline, Up To 60 Weeks (End of Study))
- Sera MOG-IgG Concentration Over Time(Baseline, Weeks 12, 24, 36, 48, 60 Weeks (End of Study))
- Number of Participants With Adverse Events Serious Adverse Events (SAEs)(Baseline, Up To 60 Weeks (End of Study))
- Number of the lesion of the MRI T2WI(Baseline, Weeks 12, 24, 36, 48, 60 Weeks (End of Study))
研究者
Chao Zhang
Professor
Tianjin Medical University General Hospital