- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT02228213
Safety and Efficacy Study of MIS416 to Treat Secondary Progressive Multiple Sclerosis
A Phase 2B Randomised, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of MIS416 in the Treatment of Subjects With Secondary Progressive Multiple Sclerosis
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
The primary objectives of the study are to:
- Determine the efficacy of MIS416, relative to placebo, when administered repeatedly via weekly intravenous (IV) administration to subjects with Secondary Progressive Multiple Sclerosis, as assessed by its effect on measures of neuromuscular function.
- Determine the safety and tolerability of a weekly regimen of MIS416.
The secondary objectives of the study are to:
- Determine the effect of MIS416 on disease activity and neurodegeneration by assessing changes in Magnetic Resonance Imaging (MRI) markers including lesions, whole brain atrophy (WBA) and Magnetization Transfer Ratio (MTR).
- Determine the effect of MIS416 on Patient Reported Outcomes (PRO) related to disability and health status.
- Assess, in a subset of subjects, the pharmacodynamic (PD) effects of MIS416, including effects on serum, Peripheral Blood Mononuclear Cell (PBMC), and Cerebral Spinal Fluid (CSF) cytokine/chemokine levels and expression patterns.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Queensland
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Brisbane, Queensland, Austrália, 4066
- The Wesley-St. Andrew's Research Institute
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South Australia
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Adelaide, South Australia, Austrália, 5000
- PARC Clinical Research
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Victoria
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Melbourne, Victoria, Austrália, 3004
- Nucleus Network - Centre for Clinical Studies
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Western Australia
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Perth, Western Australia, Austrália, 6009
- Western Australian Neuroscience Research Institute
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West Perth, Western Australia, Austrália, 6005
- Neurodegenerative Disorders Research
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Auckland, Nova Zelândia, 1010
- Optimal Clinical Trials
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Wellington, Nova Zelândia, 6021
- P3 Research
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- A historical or current cranial MRI scan demonstrating T2-hyperintense lesions consistent with MS.
- Has SPMS as determined by the 2010 Update to the McDonald Criteria
- An Expanded Disability Status Scale (EDSS) of 3.0 to 6.5 at Screening.
- Has SPMS which, in the judgment of the investigator, has been clinically active and functionally progressive within the 2 years prior to Screening
- The absence of MS relapse for at least two years prior to Baseline.
- Neurologically stable for at least four weeks prior to Screening.
Has the following laboratory values within three days prior to initiation of Investigational Product:
- Absolute neutrophil count (ANC) >= 1 x 109/L;
- Platelet count >= 100 x 109/L;
- Serum creatinine =< 1.5 mg/dL;
- Aspartate aminotransferase (AST) =<2 × upper limit of normal;
- Alanine aminotransferase (ALT) =< 2 × upper limit of normal.
- Provided written informed consent to participate.
Exclusion Criteria:
- Has primary Progressive MS (PPMS), Relapsing Remitting (RRMS), or progressive relapsing MS as determined by the 2010 update to the McDonald Criteria.
- Has not completed the discontinuation period for approved and/or investigational multiple sclerosis disease modifying therapies prior to screening.
- Has had any other immunomodulatory drug therapy or immunosuppressive therapy within four weeks prior to Screening, or systemic corticosteroids within the eight weeks prior to Screening.
- Any previous exposure to investigational MS therapeutic vaccines.
- Any use of cell-depleting monoclonal antibodies including, but not limited to, Rituximab, or Ocrelizumab.
- A diagnosis or history of collagen vascular disease (including Sjögren's syndrome and systemic lupus erythematosus), anticardiolipin antibody syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, sarcoidosis, vasculitis, Behcet's syndrome and/or Lyme disease.
- Contraindication to MRI (e.g., pacemaker or other contraindicated implanted metal device, allergy to gadolinium, or unmanageable claustrophobia).
- A history of alcohol or drug abuse (including cannabinoid use) within two years prior to Screening.
- Has had major surgery or radiation therapy within four weeks prior to Screening.
- Has an active infection requiring antibiotics within two weeks prior to Screening.
- Has had active malignancy within two years of Screening, with the exception of basal cell carcinoma and squamous cell carcinoma of the skin.
- Uncontrolled congestive heart failure, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, or transient ischemic attack within twelve weeks prior to Screening.
- Has angina, other symptomatic coronary artery disease, or known cardiomyopathy.
- Has symptomatic cardiac dysrhythmias requiring treatment, or persistent prolongation of the QTcF (Fredericia) interval to > 450 msec for males or > 470 msec for females.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Treatment
500 mcg MIS416 500 at 0.2 mg/mL administered i.v.
once weekly for 52 weeks
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Intravenous administration weekly for 52 weeks
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Comparador de Placebo: Saline
Saline administered i.v.
once weekly for 52 weeks
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Intravenous administration weekly for 52 weeks
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change from baseline of neuromuscular function at 12 months
Prazo: Baseline, 3, 6, 9 and 12 months
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Neuromuscular function will be assessed using the following test:
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Baseline, 3, 6, 9 and 12 months
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Proportion of Participants with Serious and Non-Serious Adverse Events
Prazo: Up to 12 months
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Safety assessments will be conducted at each study visit and include; characterization of the type, incidence, severity, timing, seriousness, and relationship to treatment of adverse events (AEs); effects on vital signs and clinical laboratory parameters; changes on electrocardiograms (ECGs); and at 3 months and 12 months - the number of gadolinium-enhancing lesions on cranial MRI assessments.
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Up to 12 months
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change from baseline of disability and health status at 12 months
Prazo: Baseline, 3, 6, 9, and 12 months
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Disability and health status will be assessed using the following assessments and patient reported outcomes:
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Baseline, 3, 6, 9, and 12 months
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Change from baseline of neurodegeneration by assessing changes in Magnetic Resonance Imaging (MRI) markers at 12 months
Prazo: Baseline, 3, and 12 months
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Disease activity and neurodegeneration will be assessing using Magnetic Resonance Imaging (MRI) markers including lesions, whole brain atrophy (WBA) and Magnetization Transfer Ratio (MTR).
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Baseline, 3, and 12 months
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Change from baseline of activity of immune biomarkers in serum
Prazo: Up to 1 year
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The effect on immune biomarkers will include the analysis of serum for some or all of the following markers: IP-10 (CXCL10), MCP-1 (CCL2), MIG (CXCL9), IL-8 (CXCL8), IFNγ, Neopterin, IL-1RA, sTNF-R, IL-12/23, p40, CD62E (E-selectin), CD54 (ICAM-1), and CD106 (VCAM-1).
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Up to 1 year
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Change from baseline of activity of immune biomarkers in cerebrospinal fluid (CSF)
Prazo: Up to 12 months
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The effect on immune biomarkers will include the analysis of CSF for some or all of the following markers: IP-10 (CXCL10), MCP-1 (CCL2), MIG (CXCL9), IL-8 (CXCL8), IFNγ, Neopterin, IL-1RA, sTNF-R, IL-12/23, p40, CD62E (E-selectin), CD54 (ICAM-1), and CD106 (VCAM-1).
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Up to 12 months
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Change from baseline in Peripheral Blood Mononuclear Cell (PBMC) immune biomarkers
Prazo: Up to 12 months
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Some or all of these biomarkers may be assayed ex vivo: PBMC expression of mRNA encoding proteins involved in myeloid differentiation and immune regulatory function (e.g.
VEGF, Arginine, INOS, IL-10, MMP9); PBMC myeloid subset production of IL-10, TGFβ, IL-6, TNFα, IL-1β, IFNγ, IL-17, and GM-CSF in response to stimulation with LPS, LPS/IFNγ or MIS416 ex vivo; and PBMC subset analysis of myeloid and dendritic cell subsets for immunoregulatory cell subset markers.
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Up to 12 months
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Diretor de estudo: Michael Silverman, Innate Immunotherapeutics
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Processos Patológicos
- Doenças do Sistema Nervoso
- Doenças do sistema imunológico
- Neoplasias
- Doenças Autoimunes Desmielinizantes, SNC
- Doenças Autoimunes do Sistema Nervoso
- Doenças Desmielinizantes
- Doenças autoimunes
- Processos Neoplásicos
- Esclerose múltipla
- Esclerose Múltipla Progressiva Crônica
- Esclerose
- Neoplasia Metástase
Outros números de identificação do estudo
- MIS416-202
- U1111-1166-0910 (Outro identificador: WHO)
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