Safety Study of an Immunomodulating Microparticle to Treat 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.
Secondary Progressive Multiple Sclerosis
Primary Progressive Multiple Sclerosis
|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|
- 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
- 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).
|Study Start Date:||August 2010|
|Study Completion Date:||November 2012|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
MIS416, immunomodulating microparticle, given intravenously weekly
MIS416 intravenously every week
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.
|Primorus Clinical Trials, 40 Stewart Street|
|Christchurch, Canterbury, New Zealand, 8011|
|Principal Investigator:||Alison Luckey||Primorus Clinical Trials|
|Principal Investigator:||Tim Anderson||Department of Medicine, University of Otago|