Secondary Progressive Multiple SclerosisPhase 1/2NCT01191996
Safety Study of an Immunomodulating Microparticle to Treat Progressive Multiple Sclerosis
A Phase 1/2 study testing MIS416 in people with Secondary Progressive Multiple Sclerosis and Primary Progressive Multiple Sclerosis, run by Innate Immunotherapeutics at 1 site in New Zealand.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Secondary Progressive Multiple Sclerosis, Primary Progressive Multiple Sclerosis
- What is being tested?
- MIS416
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteNew Zealand
- Study dates
- Aug 2010to Nov 2012
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
New Zealand1 site
Primorus Clinical Trials, 40 Stewart Street
Christchurch, Canterbury, 8011
About this study
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
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.
Read the 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.
- Being tested
- MIS416
- Keywords
- SPMS, PPMS, MS, Multiple Sclerosis
- 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
MIS416 intravenously every week
| Study group | Role | What they receive |
|---|---|---|
| MIS416 | Experimental | MIS416, immunomodulating microparticle, given intravenously weekly Receives: Biological: MIS416 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety profile, including maximum tolerated dose
Dose-limiting toxicities, adverse events, safety MRI assessments
Measured: 1 month in DE phase, 3 months in DC phase
Secondary outcomes (3)
Pharmacodynamic assessments
Serum and cellular immunological assays
Measured: 1 month in DE phase, 3 months in DC phase
MRI assessments
Safety MRIs
Measured: 1 month in DE phase, 3 months in DC phase
Clinical status
Neurological examination, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), Fatigue Severity Scale (FSS), Multiple Sclerosis Quality of Life (MSQLI).
Measured: 3 months in DC phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2010 (estimated)
- Study startAug 2010
- Primary completionJun 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Innate Immunotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Primorus Clinical Trials, National Multiple Sclerosis Society
- Responsible party
- Sponsor
- Investigators
- Alison Luckey, Principal investigator, Primorus Clinical TrialsTim Anderson, Principal investigator, Department of Medicine, University of Otago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01191996
- Sponsor's protocol ID
- MIS416-201
- Status last verified
- Dec 2012
- First submitted
- 30 Aug 2010
- Last updated
- 7 Dec 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 29177070Luckey 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.
PubMed 28607691
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01191996
- Acronym / sponsor ID
- MIS416-201
- Keywords
- SPMS, PPMS, MS, Multiple Sclerosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Innate ImmunotherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Primorus Clinical Trials, National Multiple Sclerosis Society
- Study start
- Aug 2010
- Primary completion
- Jun 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 31 Aug 2010 (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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MIS416 | Experimental | Biological: MIS416MIS416, immunomodulating microparticle, given intravenously weekly |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
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 |
|---|---|---|
| MIS416MIS416 intravenously every week | Biological | MIS416 |
Primary outcome
Safety profile, including maximum tolerated dose
Time frame: 1 month in DE phase, 3 months in DC phase
Dose-limiting toxicities, adverse events, safety MRI assessments
3 secondary outcomes
Pharmacodynamic assessments
Time frame: 1 month in DE phase, 3 months in DC phase
MRI assessments
Time frame: 1 month in DE phase, 3 months in DC phase
Clinical status
Time frame: 3 months in DC phase
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 7 Dec 2012.
- Derived from this study: PubMed 29177070Webster 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.
- Derived from this study: PubMed 28607691Luckey 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.
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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.
Alison Luckey principal investigator
Primorus Clinical Trials
Tim Anderson principal investigator
Department of Medicine, University of Otago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MIS416 in people with Secondary Progressive Multiple Sclerosis and Primary Progressive Multiple Sclerosis, run by Innate Immunotherapeutics at 1 site in New Zealand.
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 11 inclusion and 6 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 7 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Safety profile, including maximum tolerated dose (time frame: 1 month in DE phase, 3 months in DC phase). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01191996, which also lists 2 linked publications.
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 7 Dec 2012.