Safety Study of an Immunomodulating Microparticle to Treat Progressive Multiple Sclerosis

• Sponsor: Innate Immunotherapeutics
• Collaborators: Primorus Clinical Trials; National Multiple Sclerosis Society
• Information provided by (Responsible Party): Innate Immunotherapeutics

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.

Condition or disease	Intervention/treatment	Phase
Secondary Progressive Multiple Sclerosis; Primary Progressive Multiple Sclerosis	Biological: MIS416	Phase 1; Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	34 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	August 2010
Actual Primary Completion Date :	June 2012
Actual Study Completion Date :	November 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: MIS416; MIS416, immunomodulating microparticle, given intravenously weekly	Biological: MIS416; MIS416 intravenously every week

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. Pharmacodynamic assessments [ Time Frame: 1 month in DE phase, 3 months in DC phase ]
   Serum and cellular immunological assays
2. MRI assessments [ Time Frame: 1 month in DE phase, 3 months in DC phase ]
   Safety MRIs
3. 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).

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Locations

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New Zealand
Primorus Clinical Trials, 40 Stewart Street
Christchurch, Canterbury, New Zealand, 8011

Sponsors and Collaborators

Innate Immunotherapeutics

Primorus Clinical Trials

National Multiple Sclerosis Society

Investigators

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Principal Investigator:	Alison Luckey	Primorus Clinical Trials
Principal Investigator:	Tim Anderson	Department of Medicine, University of Otago

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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Responsible Party:	Innate Immunotherapeutics
ClinicalTrials.gov Identifier:	NCT01191996 History of Changes
Other Study ID Numbers:	MIS416-201
First Posted:	August 31, 2010
Last Update Posted:	December 7, 2012
Last Verified:	December 2012

Keywords provided by Innate Immunotherapeutics:

SPMS; PPMS; MS; Multiple Sclerosis

Additional relevant MeSH terms:

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Sclerosis; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS	Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases