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

12 juli 2017 bijgewerkt door: 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.

Studie Overzicht

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

93

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 70 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Verviervoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Treatment
500 mcg MIS416 500 at 0.2 mg/mL administered i.v. once weekly for 52 weeks
Intravenous administration weekly for 52 weeks
Placebo-vergelijker: Saline
Saline administered i.v. once weekly for 52 weeks
Intravenous administration weekly for 52 weeks
Andere namen:
  • Placebo

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change from baseline of neuromuscular function at 12 months
Tijdsspanne: 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
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change from baseline of disability and health status at 12 months
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Medewerkers

Onderzoekers

  • Studie directeur: Michael Silverman, Innate Immunotherapeutics

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 oktober 2014

Primaire voltooiing (Werkelijk)

1 mei 2017

Studie voltooiing (Werkelijk)

1 juni 2017

Studieregistratiedata

Eerst ingediend

21 augustus 2014

Eerst ingediend dat voldeed aan de QC-criteria

26 augustus 2014

Eerst geplaatst (Schatting)

28 augustus 2014

Updates van studierecords

Laatste update geplaatst (Werkelijk)

14 juli 2017

Laatste update ingediend die voldeed aan QC-criteria

12 juli 2017

Laatst geverifieerd

1 juli 2017

Meer informatie

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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