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.
Visão geral do estudo
Status
Status
Condições
Condições
Intervenção / Tratamento
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Tipo de estudo
Inscrição (Estimado)
Inscrição
Estágio
Estágio
- Fase 3
Contactos e Locais
Contato de estudo
Contato de estudo
- Nome: Huanfen Zhou, M.D.
- Número de telefone: +86 01066938024
- E-mail: zhouzhoueye@163.com
Critérios de participação
Critérios de elegibilidade
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Solteiro
Número de braços
Armas e Intervenções
Grupo de Participantes / BraçoGrupo de Participantes / Braço |
Intervenção / TratamentoIntervenção / Tratamento |
|---|---|
|
Experimental: 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. |
|
Comparador Ativo: 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. |
O que o estudo está medindo?
Medidas de resultados primários
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
the time to first adjudicated relapse from randomization
Prazo: 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
|
Medidas de resultados secundários
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Annualized relapse rate during any exposure to the experimental drugs
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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)
Prazo: 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
|
Outras medidas de resultado
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Change from baseline in Low-contrast visual acuity in affected eyes by optic neuritis at EOS visit
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
|
Colaboradores e Investigadores
Patrocinador
Patrocinador
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Início do estudo
Conclusão Primária (Estimado)
Conclusão Primária
Conclusão do estudo (Estimado)
Conclusão do estudo
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Primeira postagem
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última Atualização Postada
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
Outros números de identificação do estudo
- S2026-758-01
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