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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
93
The Wesley-St. Andrew's Research Institute
Brisbane, Queensland, Australia
PARC Clinical Research
Adelaide, South Australia, Australia
Nucleus Network - Centre for Clinical Studies
Melbourne, Victoria, Australia
Western Australian Neuroscience Research Institute
Perth, Western Australia, Australia
Change from baseline of neuromuscular function at 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);
Time frame: Baseline, 3, 6, 9 and 12 months
Proportion of Participants with Serious and Non-Serious Adverse Events
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.
Time frame: Up to 12 months
Change from baseline of disability and health status at 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).
Time frame: Baseline, 3, 6, 9, and 12 months
Change from baseline of neurodegeneration by assessing changes in Magnetic Resonance Imaging (MRI) markers at 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).
Time frame: Baseline, 3, and 12 months
Change from baseline of activity of immune biomarkers in serum
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Neurodegenerative Disorders Research
West Perth, Western Australia, Australia
Optimal Clinical Trials
Auckland, New Zealand
P3 Research
Wellington, New Zealand
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).
Time frame: Up to 1 year
Change from baseline of activity of immune biomarkers in cerebrospinal fluid (CSF)
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).
Time frame: Up to 12 months
Change from baseline in Peripheral Blood Mononuclear Cell (PBMC) immune biomarkers
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.
Time frame: Up to 12 months