Safety and Efficacy of Secukinumab Versus Mycophenolate Mofetil in Relapsing Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (SMART) (SMART)
Safety and Efficacy of Secukinumab Versus Mycophenolate Mofetil in Relapsing Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (SMART): a Multicenter, Prospective, Randomized, Controlled, Open-label, Blinded-endpoint Phase 3 Trial
The goal of this clinical trial is to evaluate the safety and efficacy of secukinumab versus mycophenolate mofetil in relapsing myelin oligodendrocyte glycoprotein antibody-associated disease.
研究概览
详细说明
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disease of the central nervous system mediated primarily by antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG). Its clinical manifestations include optic neuritis (ON), acute transverse myelitis (ATM), acute disseminated encephalomyelitis (ADEM), and, more rarely, various forms of encephalitis. Data from several cohorts suggest that approximately 50% of adult patients with MOG-IgG relapse within the first two years of disease onset. No drug is currently approved by the FDA for MOGAD, and mycophenolate mofetil (MMF) is widely used as a conventional first-line maintenance immunosuppressant. Interleukin-17A (IL-17A), a key cytokine secreted by T helper 17 (Th17) cells, participates in downstream inflammatory responses, promotes Th17 cell differentiation through a positive feedback loop, and drives the differentiation of B cells into antibody-producing plasma cells. Studies have shown that peripheral blood Th17 cell levels are significantly higher in MOGAD patients, in both the acute and remission phases, than healthy controls. Patients with higher peripheral Th17 cell counts tend to have more severe disease and higher relapse rates, suggesting that IL-17A may contribute to the pathogenesis and progression of MOGAD. Secukinumab, a humanized monoclonal antibody against the IL-17A has shown beneficial clinical effects and reduction of the risk of relapses in some patients with relapsing MOGAD in our previous pilot study. However, the efficacy and safety of secukinumab in relapsing MOGAD warrants further clinical trials.
研究类型
注册 (估计的)
阶段
- 第三阶段
联系人和位置
学习联系方式
- 姓名:Huanfen Zhou, M.D.
- 电话号码:+86 01066938024
- 邮箱:zhouzhoueye@163.com
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Key Inclusion Criteria:
Participants must meet all of the following conditions in order to be enrolled:
- 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 clear seropositive using Live cell-based assay (Live CBA);
- Expanded Disability Status Scale (EDSS) ≤7.5
- 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 the experimental drugs;
- Patients must give written informed consent.
Key Exclusion Criteria:
- Age<6 years old;
- Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of the experimental drugs;
- Individuals who are allergic to any component of the experimental drug;
- Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor;
- Treatment with tocilizumab, other IL-6/IL6-R inhibitor or JAK inhibitor within 12
- weeks or within 5 half-lives of the drug (whichever is longer) prior to Baseline;
- 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 8 weeks prior to randomization;
- Receipt of any of the following within 3 months prior to randomization: Natalizumab (Tysabri®), Methotrexate Mitoxantrone Cyclophosphamide, Eculizumab, Ofacizumab, Satolizumab, or interferon, pegylated interferon, and glatiramer acetate;
- Patients treated with cyclophosphamide, tacrolimus, everolimus, hydroxychloroquine, cyclosporine A, azathioprine, sulfasalazine within 6 months prior to Baseline;
- Patients treated with leflunomide within 8 weeks of Baseline unless a cholestyramine washout has been performed in which case the patient must be treated within 4 weeks of Baseline;
- Any other biologics within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to Baseline;
- Active ongoing diseases which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for treatment with immunomodulatory therapy;
- (8) Hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcAb) positive and peripheral blood HBV DNA positive; Individuals with positive hepatitis C virus (HCV) antibodies and positive HCV RNA; Positive for Treponema pallidum antibody; HIV antibody positive; Cytomegalovirus (CMV) DNA positive individuals;
- History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection as defined by a positive QuantiFERON TB- Gold Plus test. Patients with a positive test may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active tuberculosis. If presence of latent tuberculosis is established then treatment according to local country guidelines must be initiated prior to randomization.
- Live vaccinations within 6 weeks prior to Baseline or planned vaccination during study participation until 12 weeks after last study treatment administration.
- Other researchers have determined laboratory test results that are clinically significant and believe that the patient is not suitable to participate in this clinical trial.
- Researchers believe that participants in this clinical trial are not suitable for other reasons.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:单身的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的:secukinumab
Secukinumab 300 mg s.c. (2 x 1 mL pre-filled syringe (PFS) 150 mg secukinumab) at Baseline, Weeks 1, 2, 3, followed by administration every four weeks starting at Week 4. Secukinumab will be given in combination with a protocol-specified prednisone taper regimen. |
Secukinumab 300 mg s.c. (2 x 1 mL pre-filled syringe (PFS) 150 mg secukinumab) at Baseline, Weeks 1, 2, 3, followed by administration every four weeks starting at Week 4. Secukinumab will be given in combination with a protocol-specified prednisone taper regimen. |
|
有源比较器:mycophenolate mofetil
Mycophenolate mofetil (MMF) 1000 mg p.o. twice daily (Pediatric dose: 500-750 mg/m² body surface area, administered orally in two divided doses). MMF will be given in combination with a protocol-specified prednisone taper regimen. |
Mycophenolate mofetil (MMF) 1000 mg p.o. twice daily (Pediatric dose: 500-750 mg/m² body surface area, administered orally in two divided doses). MMF will be given in combination with a protocol-specified prednisone taper regimen. |
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
the time to first adjudicated relapse from randomization
大体时间:Baseline, Up To 48 Weeks or End of Study
|
An adjudicated relapse was defined by the protocol and positively adjudicated by the independent adjudication committee. |
Baseline, Up To 48 Weeks or End of Study
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Annualized relapse rate during any exposure to the experimental drugs
大体时间:Baseline, Up To 48 Weeks or End of Study
|
The adjudicated annualized relapse rate (ARR) was defined as the total number of protocoldefined relapses divided by the corresponding observation period in years. Before randomization, ARR was calculated as the total number of relapses before randomization divided by the time from first relapse to randomization (in days) and then divided by 365 for patients with a disease duration of ≤2 years, or as the number of relapses within the 2 years before randomization divided by 2 for patients with a disease duration of >2 years. |
Baseline, Up To 48 Weeks or End of Study
|
|
Relapse-free and steroid-free remission state at EOS visit
大体时间:48 Weeks or End of Study
|
Relapse-free and steroid-free remission state at EOS visit |
48 Weeks or End of Study
|
|
Change from baseline in dosage of prednisone at EOS visit
大体时间:Baseline, Up To 48 Weeks or End of Study
|
Change from baseline in dosage of prednisone at EOS visit |
Baseline, Up To 48 Weeks or End of Study
|
|
Change from baseline in EDSS score at EOS visit
大体时间:Baseline, Up To 48 Weeks or End of Study
|
Disease-related disability was measured by the EDSS. The EDSS was an ordinal clinical rating scale that ranges from 0 (normal neurologic examination) to 10 (death) in half-point increments. A decrease in score indicates improvement |
Baseline, Up To 48 Weeks or End of Study
|
|
Change from baseline in active MRI lesions at EOS visit
大体时间:Baseline, Up To 48 Weeks or End of Study
|
active MRI lesions: new Gd-enhancing lesions |
Baseline, Up To 48 Weeks or End of Study
|
|
Treatment-emergent adverse events (TEAEs), including treatment-emergent serious adverse events (TESAEs)
大体时间:Baseline, Up To 48 Weeks or End of Study
|
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship A SAE was any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization |
Baseline, Up To 48 Weeks or End of Study
|
其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Change from baseline in Low-contrast visual acuity in affected eyes by optic neuritis at EOS visit
大体时间:Baseline, Up To 48 Weeks or End of Study
|
Change from baseline in Low-contrast visual acuity in affected eyes by optic neuritis at EOS visit |
Baseline, Up To 48 Weeks or End of Study
|
|
Change from baseline in visual acuity in affected eyes by optic neuritis at EOS visit
大体时间:Baseline, Up To 48 Weeks or End of Study
|
om baseline in visual acuity in affected eyes by optic neuritis at EOS visit |
Baseline, Up To 48 Weeks or End of Study
|
|
Change from baseline in peripapillary retinal nerve fiber layer (pRNFL) at EOS visit
大体时间:Baseline, Up To 48 Weeks or End of Study
|
Change from baseline in peripapillary retinal nerve fiber layer (pRNFL) thickness, measured in μm by optical coherence tomography (OCT) |
Baseline, Up To 48 Weeks or End of Study
|
|
Change from baseline in ganglion cell and inner plexiform layer (GCIPL) at EOS visit
大体时间:Baseline, Up To 48 Weeks or End of Study
|
Change from baseline in ganglion cell-inner plexiform layer (GCIPL) thickness at the EOS visit, measured in μm by OCT |
Baseline, Up To 48 Weeks or End of Study
|
|
Change from baseline in ganglion cell and serum MOG-LgG titers at EOS visit
大体时间:Baseline, Up To 48 Weeks or End of Study
|
Change from baseline in serum MOG-IgG titers measured by live cell-based assay at the EOS visit |
Baseline, Up To 48 Weeks or End of Study
|
合作者和调查者
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- S2026-758-01
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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