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

Primary Purpose

Secondary Progressive Multiple Sclerosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MIS416
Saline
Sponsored by
Innate Immunotherapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Secondary Progressive Multiple Sclerosis focused on measuring multiple sclerosis, SPMS

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The Wesley-St. Andrew's Research Institute
  • PARC Clinical Research
  • Nucleus Network - Centre for Clinical Studies
  • Western Australian Neuroscience Research Institute
  • Neurodegenerative Disorders Research
  • Optimal Clinical Trials
  • P3 Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment

Saline

Arm Description

500 mcg MIS416 500 at 0.2 mg/mL administered i.v. once weekly for 52 weeks

Saline administered i.v. once weekly for 52 weeks

Outcomes

Primary Outcome Measures

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);
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.

Secondary Outcome Measures

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).
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).
Change from baseline of activity of immune biomarkers in serum
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)
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
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.

Full Information

First Posted
August 21, 2014
Last Updated
July 12, 2017
Sponsor
Innate Immunotherapeutics
Collaborators
Syneos Health
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1. Study Identification

Unique Protocol Identification Number
NCT02228213
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
October 2014 (undefined)
Primary Completion Date
May 2017 (Actual)
Study Completion Date
June 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Innate Immunotherapeutics
Collaborators
Syneos Health

4. Oversight

Data Monitoring Committee
Yes

5. 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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Secondary Progressive Multiple Sclerosis
Keywords
multiple sclerosis, SPMS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
93 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
500 mcg MIS416 500 at 0.2 mg/mL administered i.v. once weekly for 52 weeks
Arm Title
Saline
Arm Type
Placebo Comparator
Arm Description
Saline administered i.v. once weekly for 52 weeks
Intervention Type
Biological
Intervention Name(s)
MIS416
Intervention Description
Intravenous administration weekly for 52 weeks
Intervention Type
Drug
Intervention Name(s)
Saline
Other Intervention Name(s)
Placebo
Intervention Description
Intravenous administration weekly for 52 weeks
Primary Outcome Measure Information:
Title
Change from baseline of neuromuscular function at 12 months
Description
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
Title
Proportion of Participants with Serious and Non-Serious Adverse Events
Description
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
Secondary Outcome Measure Information:
Title
Change from baseline of disability and health status at 12 months
Description
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
Title
Change from baseline of neurodegeneration by assessing changes in Magnetic Resonance Imaging (MRI) markers at 12 months
Description
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
Title
Change from baseline of activity of immune biomarkers in serum
Description
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
Title
Change from baseline of activity of immune biomarkers in cerebrospinal fluid (CSF)
Description
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
Title
Change from baseline in Peripheral Blood Mononuclear Cell (PBMC) immune biomarkers
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A historical or current cranial MRI scan demonstrating T2-hyperintense lesions consistent with MS. Has SPMS as determined by the 2010 Update to the McDonald Criteria An Expanded Disability Status Scale (EDSS) of 3.0 to 6.5 at Screening. Has SPMS which, in the judgment of the investigator, has been clinically active and functionally progressive within the 2 years prior to Screening The absence of MS relapse for at least two years prior to Baseline. Neurologically stable for at least four weeks prior to Screening. 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. Provided written informed consent to participate. Exclusion Criteria: Has primary Progressive MS (PPMS), Relapsing Remitting (RRMS), or progressive relapsing MS as determined by the 2010 update to the McDonald Criteria. Has not completed the discontinuation period for approved and/or investigational multiple sclerosis disease modifying therapies prior to screening. 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. Any previous exposure to investigational MS therapeutic vaccines. Any use of cell-depleting monoclonal antibodies including, but not limited to, Rituximab, or Ocrelizumab. 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. Contraindication to MRI (e.g., pacemaker or other contraindicated implanted metal device, allergy to gadolinium, or unmanageable claustrophobia). A history of alcohol or drug abuse (including cannabinoid use) within two years prior to Screening. Has had major surgery or radiation therapy within four weeks prior to Screening. Has an active infection requiring antibiotics within two weeks prior to Screening. Has had active malignancy within two years of Screening, with the exception of basal cell carcinoma and squamous cell carcinoma of the skin. Uncontrolled congestive heart failure, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, or transient ischemic attack within twelve weeks prior to Screening. Has angina, other symptomatic coronary artery disease, or known cardiomyopathy. Has symptomatic cardiac dysrhythmias requiring treatment, or persistent prolongation of the QTcF (Fredericia) interval to > 450 msec for males or > 470 msec for females.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Silverman
Organizational Affiliation
Innate Immunotherapeutics
Official's Role
Study Director
Facility Information:
Facility Name
The Wesley-St. Andrew's Research Institute
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4066
Country
Australia
Facility Name
PARC Clinical Research
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Nucleus Network - Centre for Clinical Studies
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Western Australian Neuroscience Research Institute
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Neurodegenerative Disorders Research
City
West Perth
State/Province
Western Australia
ZIP/Postal Code
6005
Country
Australia
Facility Name
Optimal Clinical Trials
City
Auckland
ZIP/Postal Code
1010
Country
New Zealand
Facility Name
P3 Research
City
Wellington
ZIP/Postal Code
6021
Country
New Zealand

12. IPD Sharing Statement

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

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