Safety Study of an Immunomodulating Microparticle to Treat Progressive Multiple Sclerosis
Primary Purpose
Secondary Progressive Multiple Sclerosis, Primary Progressive Multiple Sclerosis
Status
Completed
Phase
Phase 1
Locations
New Zealand
Study Type
Interventional
Intervention
MIS416
Sponsored by
About this trial
This is an interventional treatment trial for Secondary Progressive Multiple Sclerosis focused on measuring SPMS, PPMS, MS, Multiple Sclerosis
Eligibility Criteria
Inclusion Criteria:
- At least 18 years of age.
- Diagnosis of MS, by the McDonald criteria.
- Chronic progressive MS (CPMS), defined as either primary progressive MS (PPMS) or secondary progressive MS (SPMS), per the criteria of the National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. [NOTE: In the dose-confirmation phase, only subjects with SPMS may be enrolled].
- MS is clinically active with worsening clinical status within the past 2 years, defined as an increase in EDSS by 1 point or more, sustained for at least 6 months.
- Expanded Disability Status Scale (EDSS) of 2.5 to 7.0 at Screening.
The following laboratory values must be documented within 3 days prior to initiation of study drug:
- Absolute neutrophil count (ANC) >= 1 x 109/L
- Platelet count >= 100 x 109/L
- Serum creatinine =< 1.5 mg/dL
- AST (SGOT) and ALT (SGPT) =< 2 × upper limit of normal.
- Provide written informed consent to participate.
Exclusion Criteria:
- Relapsing-remitting MS or progressive-relapsing MS
- Any immunomodulatory drug therapy or immunosuppressive therapy within the previous six months, or vaccine or systemic corticosteroids within the previous 60 days, prior to initiation of study drug.
- Exposure to other experimental treatments currently under investigation in MS clinical trials, including alemtuzamab, rituximab, fingolimod, and clabribine.
- 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 (CADASIL), sarcoidosis, vasculitis, Bechet's syndrome and/or Lyme disease.
- History of alcohol or drug abuse (with the exception of cannabinoids) within 2 years prior to initiation of study drug.
- Previous exposure to MIS416.
Sites / Locations
- Primorus Clinical Trials, 40 Stewart Street
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
MIS416
Arm Description
MIS416, immunomodulating microparticle, given intravenously weekly
Outcomes
Primary Outcome Measures
Safety profile, including maximum tolerated dose
Dose-limiting toxicities, adverse events, safety MRI assessments
Secondary Outcome Measures
Pharmacodynamic assessments
Serum and cellular immunological assays
MRI assessments
Safety MRIs
Clinical status
Neurological examination, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), Fatigue Severity Scale (FSS), Multiple Sclerosis Quality of Life (MSQLI).
Full Information
NCT ID
NCT01191996
First Posted
August 30, 2010
Last Updated
December 5, 2012
Sponsor
Innate Immunotherapeutics
Collaborators
Primorus Clinical Trials, National Multiple Sclerosis Society
1. Study Identification
Unique Protocol Identification Number
NCT01191996
Brief Title
Safety Study of an Immunomodulating Microparticle to Treat Progressive Multiple Sclerosis
Official Title
A Phase 2, Open-label, Dose-escalation Study Evaluating the Safety, Tolerability, and Pharmacodynamics of Intravenously Administered MIS416 in Patients With Chronic Progressive Multiple Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
November 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Innate Immunotherapeutics
Collaborators
Primorus Clinical Trials, National Multiple Sclerosis Society
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of the study is to determine the safety and tolerability, dose-limiting toxicities, maximum tolerated dose, and recommended therapeutic dose of intravenously administered MIS416 weekly in patients with chronic progressive multiple sclerosis.
Detailed Description
This is a single center, open-label, non-randomized, dose-escalation study, to be conducted in two phases:
a dose-escalation (DE) phase, to evaluate the safety, tolerability, MTD, and PD of MIS416 administered IV once weekly for 4 doses; and
a dose-confirmation (DC) phase, which will be a cohort expansion at or below the MTD (i.e., the RTD) of MIS416, dosed once weekly for up to 12 doses.
Subjects will be treated with a weekly IV dose of MIS416 in 28-day cycles: 1 cycle in the DE phase, and up to 3 cycles in the DC phase. Subjects will be evaluated and dosed weekly each cycle in each phase. Subjects will return for a follow-up visit 7 days after completion of the last dose of study drug.
The primary objectives of this study are:
To determine the safety and tolerability, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended therapeutic dose (RTD) of intravenously (IV) administered MIS416 weekly in patients with chronic progressive multiple sclerosis (CPMS); and
To assess the pharmacodynamic (PD) effects of MIS416, including effects on serum cytokine levels and peripheral blood mononuclear cell (PBMC) composition, cytokine/chemokine expression and function.
The secondary objectives of this study are:
To document any changes in MS clinical status occurring during the 12-week MIS416 dosing period in the dose-confirmation phase, as determined by the Multiple Sclerosis Functional Composite (MSFC), Fatigue Severity Scale (FSS), Short Form Health Survey (SF-36), and Expanded Disability Status Scale (EDSS); the frequency of clinical relapses; and signs of clinical activity on serial cranial MRI scans; and
To evaluate, in exploratory fashion, any correlations between clinical, radiological and PD outcomes.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Secondary Progressive Multiple Sclerosis, Primary Progressive Multiple Sclerosis
Keywords
SPMS, PPMS, MS, Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MIS416
Arm Type
Experimental
Arm Description
MIS416, immunomodulating microparticle, given intravenously weekly
Intervention Type
Biological
Intervention Name(s)
MIS416
Intervention Description
MIS416 intravenously every week
Primary Outcome Measure Information:
Title
Safety profile, including maximum tolerated dose
Description
Dose-limiting toxicities, adverse events, safety MRI assessments
Time Frame
1 month in DE phase, 3 months in DC phase
Secondary Outcome Measure Information:
Title
Pharmacodynamic assessments
Description
Serum and cellular immunological assays
Time Frame
1 month in DE phase, 3 months in DC phase
Title
MRI assessments
Description
Safety MRIs
Time Frame
1 month in DE phase, 3 months in DC phase
Title
Clinical status
Description
Neurological examination, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), Fatigue Severity Scale (FSS), Multiple Sclerosis Quality of Life (MSQLI).
Time Frame
3 months in DC phase
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
At least 18 years of age.
Diagnosis of MS, by the McDonald criteria.
Chronic progressive MS (CPMS), defined as either primary progressive MS (PPMS) or secondary progressive MS (SPMS), per the criteria of the National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. [NOTE: In the dose-confirmation phase, only subjects with SPMS may be enrolled].
MS is clinically active with worsening clinical status within the past 2 years, defined as an increase in EDSS by 1 point or more, sustained for at least 6 months.
Expanded Disability Status Scale (EDSS) of 2.5 to 7.0 at Screening.
The following laboratory values must be documented within 3 days prior to initiation of study drug:
Absolute neutrophil count (ANC) >= 1 x 109/L
Platelet count >= 100 x 109/L
Serum creatinine =< 1.5 mg/dL
AST (SGOT) and ALT (SGPT) =< 2 × upper limit of normal.
Provide written informed consent to participate.
Exclusion Criteria:
Relapsing-remitting MS or progressive-relapsing MS
Any immunomodulatory drug therapy or immunosuppressive therapy within the previous six months, or vaccine or systemic corticosteroids within the previous 60 days, prior to initiation of study drug.
Exposure to other experimental treatments currently under investigation in MS clinical trials, including alemtuzamab, rituximab, fingolimod, and clabribine.
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 (CADASIL), sarcoidosis, vasculitis, Bechet's syndrome and/or Lyme disease.
History of alcohol or drug abuse (with the exception of cannabinoids) within 2 years prior to initiation of study drug.
Previous exposure to MIS416.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alison Luckey
Organizational Affiliation
Primorus Clinical Trials
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Tim Anderson
Organizational Affiliation
Department of Medicine, University of Otago
Official's Role
Principal Investigator
Facility Information:
Facility Name
Primorus Clinical Trials, 40 Stewart Street
City
Christchurch
State/Province
Canterbury
ZIP/Postal Code
8011
Country
New Zealand
12. IPD Sharing Statement
Citations:
PubMed Identifier
29177070
Citation
Webster GA, Sim DA, La Flamme AC, Mayo NE. Evaluation of neurological changes in secondary progressive multiple sclerosis patients treated with immune modulator MIS416: results from a feasibility study. Pilot Feasibility Stud. 2017 Nov 16;3:60. doi: 10.1186/s40814-017-0201-4. eCollection 2017.
Results Reference
derived
PubMed Identifier
28607691
Citation
Luckey AM, Anderson T, Silverman MH, Webster G. Safety, tolerability and pharmacodynamics of a novel immunomodulator, MIS416, in patients with chronic progressive multiple sclerosis. Mult Scler J Exp Transl Clin. 2015 May 12;1:2055217315583385. doi: 10.1177/2055217315583385. eCollection 2015 Jan-Dec.
Results Reference
derived
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Safety Study of an Immunomodulating Microparticle to Treat Progressive Multiple Sclerosis
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