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.
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
詳細な説明
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.
研究の種類
研究の種類
入学 (推定)
入学
段階
段階
- フェーズ 3
連絡先と場所
研究連絡先
研究連絡先
- 名前:Huanfen Zhou, M.D.
- 電話番号:+86 01066938024
- メール:zhouzhoueye@163.com
参加基準
適格基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:独身
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
|
実験的: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. |
|
アクティブコンパレータ: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. |
この研究は何を測定していますか?
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
the time to first adjudicated relapse from randomization
時間枠: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
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Annualized relapse rate during any exposure to the experimental drugs
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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)
時間枠: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
|
その他の成果指標
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change from baseline in Low-contrast visual acuity in affected eyes by optic neuritis at EOS visit
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
|
協力者と研究者
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (推定)
研究開始
一次修了 (推定)
一次修了
研究の完了 (推定)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (実際)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
QC基準を満たした最後の更新が送信されました
最終確認日
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
その他の研究ID番号
- S2026-758-01
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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