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Safety Study of an Immunomodulating Microparticle to Treat Progressive Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT01191996
Recruitment Status : Completed
First Posted : August 31, 2010
Last Update Posted : December 7, 2012
Sponsor:
Collaborators:
Primorus Clinical Trials
National Multiple Sclerosis Society
Information provided by (Responsible Party):
Innate Immunotherapeutics

Tracking Information
First Submitted Date  ICMJE August 30, 2010
First Posted Date  ICMJE August 31, 2010
Last Update Posted Date December 7, 2012
Study Start Date  ICMJE August 2010
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 10, 2011)
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
Original Primary Outcome Measures  ICMJE
 (submitted: August 30, 2010)
Safety profile, including maximum tolerated dose [ Time Frame: 1 month in DE phase, 6 months in DC phase ]
Dose-limiting toxicities, adverse events, safety MRI assessments
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2011)
  • Pharmacodynamic assessments [ Time Frame: 1 month in DE phase, 3 months in DC phase ]
    Serum and cellular immunological assays
  • MRI assessments [ Time Frame: 1 month in DE phase, 3 months in DC phase ]
    Safety MRIs
  • Clinical status [ Time Frame: 3 months in DC phase ]
    Neurological examination, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), Fatigue Severity Scale (FSS), Multiple Sclerosis Quality of Life (MSQLI).
Original Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2010)
  • Pharmacodynamic assessments [ Time Frame: 1 month in DE phase, 6 months in DC phase ]
    Serum and cellular immunological assays
  • MRI assessments [ Time Frame: 1 month in DE phase, 6 months in DC phase ]
    Safety MRIs
  • Clinical status [ Time Frame: 6 months in DC phase ]
    Neurological examination, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of an Immunomodulating Microparticle to Treat Progressive Multiple Sclerosis
Official Title  ICMJE 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
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:

  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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Secondary Progressive Multiple Sclerosis
  • Primary Progressive Multiple Sclerosis
Intervention  ICMJE Biological: MIS416
MIS416 intravenously every week
Study Arms  ICMJE Experimental: MIS416
MIS416, immunomodulating microparticle, given intravenously weekly
Intervention: Biological: MIS416
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 5, 2012)
34
Original Estimated Enrollment  ICMJE
 (submitted: August 30, 2010)
24
Actual Study Completion Date  ICMJE November 2012
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE New Zealand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01191996
Other Study ID Numbers  ICMJE MIS416-201
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Innate Immunotherapeutics
Study Sponsor  ICMJE Innate Immunotherapeutics
Collaborators  ICMJE
  • Primorus Clinical Trials
  • National Multiple Sclerosis Society
Investigators  ICMJE
Principal Investigator: Alison Luckey Primorus Clinical Trials
Principal Investigator: Tim Anderson Department of Medicine, University of Otago
PRS Account Innate Immunotherapeutics
Verification Date December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP