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History of Changes for Study: NCT02228213
Safety and Efficacy Study of MIS416 to Treat Secondary Progressive Multiple Sclerosis
Latest version (submitted July 12, 2017) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 26, 2014 None (earliest Version on record)
2 September 21, 2014 Contacts/Locations and Study Status
3 September 25, 2014 Contacts/Locations and Study Status
4 January 14, 2015 Study Status, Contacts/Locations and Study Identification
5 February 19, 2015 Eligibility and Study Status
6 March 11, 2015 Study Status and Contacts/Locations
7 March 26, 2015 Contacts/Locations and Study Status
8 August 27, 2015 Contacts/Locations and Study Status
9 April 22, 2016 Recruitment Status, Study Status, Contacts/Locations and Study Design
10 June 15, 2016 Study Status
11 July 12, 2017 Recruitment Status and Study Status
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Study NCT02228213
Submitted Date:  August 26, 2014 (v1)

Open or close this module Study Identification
Unique Protocol ID: MIS416-202
Brief Title: Safety and Efficacy Study of MIS416 to Treat Secondary Progressive Multiple Sclerosis
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
Secondary IDs:
Open or close this module Study Status
Record Verification: August 2014
Overall Status: Recruiting
Study Start: August 2014
Primary Completion: December 2015 [Anticipated]
Study Completion: December 2015 [Anticipated]
First Submitted: August 21, 2014
First Submitted that
Met QC Criteria:
August 26, 2014
First Posted: August 28, 2014 [Estimate]
Last Update Submitted that
Met QC Criteria:
August 26, 2014
Last Update Posted: August 28, 2014 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Innate Immunotherapeutics
Responsible Party: Sponsor
Collaborators: Syneos Health
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: 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.
Detailed Description:

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.
Open or close this module Conditions
Conditions: Secondary Progressive Multiple Sclerosis
Keywords: multiple sclerosis
SPMS
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 90 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Treatment
500 mcg MIS416 500 at 0.2 mg/mL administered i.v. once weekly for 52 weeks
Biological: MIS416
Intravenous administration weekly for 52 weeks
Placebo Comparator: Saline
Saline administered i.v. once weekly for 52 weeks
Drug: Saline
Intravenous administration weekly for 52 weeks
Other Names:
  • Placebo
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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);
2. 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.
Secondary Outcome Measures:
1. 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).
2. 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).
3. 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).
4. 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).
5. 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.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 65 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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. An increase in at least 1.0 point in the EDSS in the previous two years if the EDSS at Screening is 3.0 - 5.5, or of at least 0.5 points if the EDSS at Screening is 6.0 - 6.5.
  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.
Open or close this module Contacts/Locations
Study Officials: Jason Burton
Principal Investigator
Western Australian Neuroscience Research Institute
Locations: Australia, Western Australia
Western Australian Neuroscience Research Institute
[Recruiting]
Perth, Western Australia, Australia, 6009
Contact:Contact: Susan Walters +61 (8) 9346 4884 susan.walters@health.wa.gov.au
Contact:Principal Investigator: Jason Burton
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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