Safety and Efficacy Study of MIS416 to Treat Secondary Progressive Multiple Sclerosis
Secondary Progressive Multiple Sclerosis
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||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|
- Change from baseline of neuromuscular function at 12 months [ Time Frame: 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);
- Proportion of Participants with Serious and Non-Serious Adverse Events [ Time Frame: 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.
- Change from baseline of disability and health status at 12 months [ Time Frame: 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).
- Change from baseline of neurodegeneration by assessing changes in Magnetic Resonance Imaging (MRI) markers at 12 months [ Time Frame: 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).
- Change from baseline of activity of immune biomarkers in serum [ Time Frame: 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).
- Change from baseline of activity of immune biomarkers in cerebrospinal fluid (CSF) [ Time Frame: 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).
- Change from baseline in Peripheral Blood Mononuclear Cell (PBMC) immune biomarkers [ Time Frame: 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.
|Study Start Date:||October 2014|
|Estimated Study Completion Date:||September 2017|
|Estimated Primary Completion Date:||May 2017 (Final data collection date for primary outcome measure)|
500 mcg MIS416 500 at 0.2 mg/mL administered i.v. once weekly for 52 weeks
Intravenous administration weekly for 52 weeks
Placebo Comparator: Saline
Saline administered i.v. once weekly for 52 weeks
Intravenous administration weekly for 52 weeks
Other Name: Placebo
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02228213
|The Wesley-St. Andrew's Research Institute|
|Brisbane, Queensland, Australia, 4066|
|Australia, South Australia|
|PARC Clinical Research|
|Adelaide, South Australia, Australia, 5000|
|Nucleus Network - Centre for Clinical Studies|
|Melbourne, Victoria, Australia, 3004|
|Australia, Western Australia|
|Western Australian Neuroscience Research Institute|
|Perth, Western Australia, Australia, 6009|
|Neurodegenerative Disorders Research|
|West Perth, Western Australia, Australia, 6005|
|Optimal Clinical Trials|
|Auckland, New Zealand, 1010|
|Wellington, New Zealand, 6021|
|Study Director:||Michael Silverman||Innate Immunotherapeutics|