Secondary Progressive Multiple SclerosisPhase 2NCT02228213
Safety and Efficacy Study of MIS416 to Treat Secondary Progressive Multiple Sclerosis
A Phase 2 study testing MIS416 and Saline in people with Secondary Progressive Multiple Sclerosis, run by Innate Immunotherapeutics at 7 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Secondary Progressive Multiple Sclerosis
- What is being tested?
- MIS416 and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 93 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Oct 2014to Jun 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Australia5 sites
PARC Clinical Research
Adelaide, South Australia, 5000
The Wesley-St. Andrew's Research Institute
Brisbane, Queensland, 4066
Nucleus Network - Centre for Clinical Studies
Melbourne, Victoria, 3004
Western Australian Neuroscience Research Institute
Perth, Western Australia, 6009
Neurodegenerative Disorders Research
West Perth, Western Australia, 6005
New Zealand2 sites
Optimal Clinical Trials
Auckland, 1010
P3 Research
Wellington, 6021
About this study
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
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.
Read the 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.
- Conditions
- Secondary Progressive Multiple Sclerosis
- Being tested
- MIS416, Saline
- Keywords
- multiple sclerosis, SPMS
- Medical subject headings
- Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MIS416Biological
Intravenous administration weekly for 52 weeks
SalineDrug
Also called Placebo
Intravenous administration weekly for 52 weeks
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | 500 mcg MIS416 500 at 0.2 mg/mL administered i.v. once weekly for 52 weeks Receives: Biological: MIS416 |
| Saline | Placebo comparator | Saline administered i.v. once weekly for 52 weeks Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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);
Measured: 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.
Measured: Up to 12 months
Secondary outcomes (5)
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).
Measured: 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).
Measured: Baseline, 3, and 12 months
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).
Measured: 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).
Measured: 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.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2014 (estimated)
- Study startOct 2014
- Primary completionMay 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Secondary Progressive Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Innate Immunotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Syneos Health
- Responsible party
- Sponsor
- Investigators
- Michael Silverman, Study director, Innate Immunotherapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02228213
- Sponsor's protocol ID
- MIS416-202
- Other IDs
- U1111-1166-0910
- Status last verified
- Jul 2017
- First submitted
- 21 Aug 2014
- Last updated
- 14 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02228213
- Acronym / sponsor ID
- MIS416-202
- Conditions
- Secondary Progressive Multiple Sclerosis
- Keywords
- multiple sclerosis, SPMS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Innate ImmunotherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Syneos Health
- Study start
- Oct 2014
- Primary completion
- May 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 28 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Biological: MIS416500 mcg MIS416 500 at 0.2 mg/mL administered i.v. once weekly for 52 weeks |
| Saline | Placebo comparator | Drug: SalineSaline administered i.v. once weekly for 52 weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MIS416Intravenous administration weekly for 52 weeks | Biological | Treatment |
| SalineAlso: PlaceboIntravenous administration weekly for 52 weeks | Drug | Saline |
Primary outcome
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.
5 secondary outcomes
Change from baseline of disability and health status at 12 months
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
Time frame: Baseline, 3, and 12 months
Change from baseline of activity of immune biomarkers in serum
Time frame: Up to 1 year
Change from baseline of activity of immune biomarkers in cerebrospinal fluid (CSF)
Time frame: Up to 12 months
Change from baseline in Peripheral Blood Mononuclear Cell (PBMC) immune biomarkers
Time frame: Up to 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Silverman study director
Innate Immunotherapeutics
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MIS416 and Saline in people with Secondary Progressive Multiple Sclerosis, run by Innate Immunotherapeutics at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline of neuromuscular function at 12 months (time frame: Baseline, 3, 6, 9 and 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2017.