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

12 de julio de 2017 actualizado 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.

Descripción general del estudio

Estado

Terminado

Intervención / Tratamiento

Descripción detallada

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 estudio

Intervencionista

Inscripción (Actual)

93

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

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

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 70 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
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 placebos: Saline
Saline administered i.v. once weekly for 52 weeks
Intravenous administration weekly for 52 weeks
Otros nombres:
  • Placebo

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Change from baseline of neuromuscular function at 12 months
Periodo de tiempo: 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
Periodo de tiempo: 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 resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Change from baseline of disability and health status at 12 months
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Colaboradores

Investigadores

  • Director de estudio: Michael Silverman, Innate Immunotherapeutics

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de octubre de 2014

Finalización primaria (Actual)

1 de mayo de 2017

Finalización del estudio (Actual)

1 de junio de 2017

Fechas de registro del estudio

Enviado por primera vez

21 de agosto de 2014

Primero enviado que cumplió con los criterios de control de calidad

26 de agosto de 2014

Publicado por primera vez (Estimar)

28 de agosto de 2014

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

14 de julio de 2017

Última actualización enviada que cumplió con los criterios de control de calidad

12 de julio de 2017

Última verificación

1 de julio de 2017

Más información

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

Ensayos clínicos sobre MIS416

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