Safety Study of an Immunomodulating Microparticle to Treat Progressive Multiple Sclerosis - Full Text View

Purpose

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	Intervention	Phase
Secondary Progressive Multiple Sclerosis Primary Progressive Multiple Sclerosis	Biological: MIS416	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: multiple sclerosis

MedlinePlus related topics: Multiple Sclerosis

U.S. FDA Resources

Further study details as provided by Innate Immunotherapeutics:

Primary Outcome Measures:

Safety profile, including maximum tolerated dose [ Time Frame: 1 month in DE phase, 3 months in DC phase ] [ Designated as safety issue: Yes ]
Dose-limiting toxicities, adverse events, safety MRI assessments

Secondary Outcome Measures:

Pharmacodynamic assessments [ Time Frame: 1 month in DE phase, 3 months in DC phase ] [ Designated as safety issue: Yes ]
Serum and cellular immunological assays
MRI assessments [ Time Frame: 1 month in DE phase, 3 months in DC phase ] [ Designated as safety issue: Yes ]
Safety MRIs
Clinical status [ Time Frame: 3 months in DC phase ] [ Designated as safety issue: No ]
Neurological examination, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), Fatigue Severity Scale (FSS), Multiple Sclerosis Quality of Life (MSQLI).


Enrollment:	34
Study Start Date:	August 2010
Study Completion Date:	November 2012
Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: MIS416 MIS416, immunomodulating microparticle, given intravenously weekly	Biological: MIS416 MIS416 intravenously every week

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01191996

Locations


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


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

More Information


Responsible Party:	Innate Immunotherapeutics
ClinicalTrials.gov Identifier:	NCT01191996 History of Changes
Other Study ID Numbers:	MIS416-201
Study First Received:	August 30, 2010
Last Updated:	December 5, 2012
Health Authority:	New Zealand: Ministry of Health

Keywords provided by Innate Immunotherapeutics:


SPMS PPMS MS Multiple Sclerosis

Additional relevant MeSH terms:


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

ClinicalTrials.gov processed this record on September 23, 2016