Safety Study of an Immunomodulating Microparticle to Treat Progressive Multiple Sclerosis

NCT ID: NCT01191996

Last Updated: 2012-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-08-31

Study Completion Date

2012-11-30

Brief Summary

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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

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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:

1. 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
2. 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:

1. 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
2. To evaluate, in exploratory fashion, any correlations between clinical, radiological and PD outcomes.

Conditions

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Secondary Progressive Multiple Sclerosis Primary Progressive Multiple Sclerosis

Keywords

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SPMS PPMS MS Multiple Sclerosis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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MIS416

MIS416, immunomodulating microparticle, given intravenously weekly

Group Type EXPERIMENTAL

MIS416

Intervention Type BIOLOGICAL

MIS416 intravenously every week

Interventions

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MIS416

MIS416 intravenously every week

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Primorus Clinical Trials

UNKNOWN

Sponsor Role collaborator

National Multiple Sclerosis Society

OTHER

Sponsor Role collaborator

Innate Immunotherapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alison Luckey

Role: PRINCIPAL_INVESTIGATOR

Primorus Clinical Trials

Tim Anderson

Role: PRINCIPAL_INVESTIGATOR

Department of Medicine, University of Otago

Locations

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Primorus Clinical Trials, 40 Stewart Street

Christchurch, Canterbury, New Zealand

Site Status

Countries

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New Zealand

References

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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.

Reference Type DERIVED
PMID: 29177070 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28607691 (View on PubMed)

Other Identifiers

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MIS416-201

Identifier Type: -

Identifier Source: org_study_id