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Safety and Efficacy Study of MIS416 to Treat Secondary Progressive Multiple Sclerosis

12 de julho de 2017 atualizado por: Innate Immunotherapeutics

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

The purpose of this study is to determine whether MIS416 administered once weekly over 12 months is safe, tolerable, and improves a range of signs and symptoms associated with secondary progressive multiple sclerosis.

Visão geral do estudo

Status

Concluído

Descrição detalhada

The primary objectives of the study are to:

  1. 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.
  2. Determine the safety and tolerability of a weekly regimen of MIS416.

The secondary objectives of the study are to:

  1. 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).
  2. Determine the effect of MIS416 on Patient Reported Outcomes (PRO) related to disability and health status.
  3. 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

Intervencional

Inscrição (Real)

93

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

    • Queensland
      • Brisbane, Queensland, Austrália, 4066
        • The Wesley-St. Andrew's Research Institute
    • South Australia
      • Adelaide, South Australia, Austrália, 5000
        • PARC Clinical Research
    • Victoria
      • Melbourne, Victoria, Austrália, 3004
        • Nucleus Network - Centre for Clinical Studies
    • Western Australia
      • Perth, Western Australia, Austrália, 6009
        • Western Australian Neuroscience Research Institute
      • West Perth, Western Australia, Austrália, 6005
        • Neurodegenerative Disorders Research
      • Auckland, Nova Zelândia, 1010
        • Optimal Clinical Trials
      • Wellington, Nova Zelândia, 6021
        • P3 Research

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 70 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  1. A historical or current cranial MRI scan demonstrating T2-hyperintense lesions consistent with MS.
  2. Has SPMS as determined by the 2010 Update to the McDonald Criteria
  3. An Expanded Disability Status Scale (EDSS) of 3.0 to 6.5 at Screening.
  4. Has SPMS which, in the judgment of the investigator, has been clinically active and functionally progressive within the 2 years prior to Screening
  5. The absence of MS relapse for at least two years prior to Baseline.
  6. Neurologically stable for at least four weeks prior to Screening.
  7. 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.
  8. Provided written informed consent to participate.

Exclusion Criteria:

  1. Has primary Progressive MS (PPMS), Relapsing Remitting (RRMS), or progressive relapsing MS as determined by the 2010 update to the McDonald Criteria.
  2. Has not completed the discontinuation period for approved and/or investigational multiple sclerosis disease modifying therapies prior to screening.
  3. 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.
  4. Any previous exposure to investigational MS therapeutic vaccines.
  5. Any use of cell-depleting monoclonal antibodies including, but not limited to, Rituximab, or Ocrelizumab.
  6. 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.
  7. Contraindication to MRI (e.g., pacemaker or other contraindicated implanted metal device, allergy to gadolinium, or unmanageable claustrophobia).
  8. A history of alcohol or drug abuse (including cannabinoid use) within two years prior to Screening.
  9. Has had major surgery or radiation therapy within four weeks prior to Screening.
  10. Has an active infection requiring antibiotics within two weeks prior to Screening.
  11. Has had active malignancy within two years of Screening, with the exception of basal cell carcinoma and squamous cell carcinoma of the skin.
  12. Uncontrolled congestive heart failure, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, or transient ischemic attack within twelve weeks prior to Screening.
  13. Has angina, other symptomatic coronary artery disease, or known cardiomyopathy.
  14. 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

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

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
Experimental: Treatment
500 mcg MIS416 500 at 0.2 mg/mL administered i.v. once weekly for 52 weeks
Intravenous administration weekly for 52 weeks
Comparador de Placebo: Saline
Saline administered i.v. once weekly for 52 weeks
Intravenous administration weekly for 52 weeks
Outros nomes:
  • Placebo

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Change from baseline of neuromuscular function at 12 months
Prazo: Baseline, 3, 6, 9 and 12 months

Neuromuscular function will be assessed using the following test:

  • MS Function Composite (MSFC), comprising the; timed 25 Foot Walk, 9 Hole Peg Test (9HPT), and Paced Auditory Serial Addition Test (PASAT);
  • Jebsen Hand Function Test (JHFT);
  • Grip, tip and key pinch strength;
  • Symbol digit modalities test (SDMT);
  • Sloan low-contrast letter visual acuity (SLCVA);
  • 6-minute walk test (6MWT);
Baseline, 3, 6, 9 and 12 months
Proportion of Participants with Serious and Non-Serious Adverse Events
Prazo: Up to 12 months
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.
Up to 12 months

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Change from baseline of disability and health status at 12 months
Prazo: Baseline, 3, 6, 9, and 12 months

Disability and health status will be assessed using the following assessments and patient reported outcomes:

  • Expanded Disability Status Scale (EDSS)
  • Patient Reported Outcomes (PROs) including;

    • SF-36 and its components;
    • MS Impact Scale (MSIS-29);
    • Neurological Fatigue Index for MS (NFI-MS);
    • Brief Pain Inventory (BPI).
Baseline, 3, 6, 9, and 12 months
Change from baseline of neurodegeneration by assessing changes in Magnetic Resonance Imaging (MRI) markers at 12 months
Prazo: Baseline, 3, and 12 months
Disease activity and neurodegeneration will be assessing using Magnetic Resonance Imaging (MRI) markers including lesions, whole brain atrophy (WBA) and Magnetization Transfer Ratio (MTR).
Baseline, 3, and 12 months
Change from baseline of activity of immune biomarkers in serum
Prazo: Up to 1 year
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).
Up to 1 year
Change from baseline of activity of immune biomarkers in cerebrospinal fluid (CSF)
Prazo: Up to 12 months
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).
Up to 12 months
Change from baseline in Peripheral Blood Mononuclear Cell (PBMC) immune biomarkers
Prazo: Up to 12 months
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.
Up to 12 months

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Colaboradores

Investigadores

  • Diretor de estudo: Michael Silverman, Innate Immunotherapeutics

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de outubro de 2014

Conclusão Primária (Real)

1 de maio de 2017

Conclusão do estudo (Real)

1 de junho de 2017

Datas de inscrição no estudo

Enviado pela primeira vez

21 de agosto de 2014

Enviado pela primeira vez que atendeu aos critérios de CQ

26 de agosto de 2014

Primeira postagem (Estimativa)

28 de agosto de 2014

Atualizações de registro de estudo

Última Atualização Postada (Real)

14 de julho de 2017

Última atualização enviada que atendeu aos critérios de controle de qualidade

12 de julho de 2017

Última verificação

1 de julho de 2017

Mais Informações

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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