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Safety Study of an Immunomodulating Microparticle to Treat Progressive Multiple Sclerosis

Primary Purpose

Secondary Progressive Multiple Sclerosis, Primary Progressive Multiple Sclerosis

Status

Completed

Phase

Phase 1

Locations

New Zealand

Study Type

Interventional

Intervention

MIS416

About this trial

This is an interventional treatment trial for Secondary Progressive Multiple Sclerosis focused on measuring SPMS, PPMS, MS, Multiple Sclerosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Primorus Clinical Trials, 40 Stewart Street

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MIS416

Arm Description

MIS416, immunomodulating microparticle, given intravenously weekly

Outcomes

Primary Outcome Measures

Safety profile, including maximum tolerated dose

Dose-limiting toxicities, adverse events, safety MRI assessments

Secondary Outcome Measures

Pharmacodynamic assessments

Serum and cellular immunological assays

MRI assessments

Safety MRIs

Clinical status

Neurological examination, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), Fatigue Severity Scale (FSS), Multiple Sclerosis Quality of Life (MSQLI).

Full Information

NCT ID

NCT01191996

First Posted

August 30, 2010

Last Updated

December 5, 2012

Sponsor

Innate Immunotherapeutics

Collaborators

Primorus Clinical Trials, National Multiple Sclerosis Society

1. Study Identification

Unique Protocol Identification Number

NCT01191996

Brief Title

Safety Study of an Immunomodulating Microparticle to Treat Progressive Multiple Sclerosis

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 Type

Interventional

2. Study Status

Record Verification Date

December 2012

Overall Recruitment Status

Completed

Study Start Date

August 2010 (undefined)

Primary Completion Date

June 2012 (Actual)

Study Completion Date

November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Innate Immunotherapeutics

Collaborators

Primorus Clinical Trials, National Multiple Sclerosis Society

4. Oversight

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Secondary Progressive Multiple Sclerosis, Primary Progressive Multiple Sclerosis

Keywords

SPMS, PPMS, MS, Multiple Sclerosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MIS416

Arm Type

Experimental

Arm Description

MIS416, immunomodulating microparticle, given intravenously weekly

Intervention Type

Biological

Intervention Name(s)

MIS416

Intervention Description

MIS416 intravenously every week

Primary Outcome Measure Information:

Title

Safety profile, including maximum tolerated dose

Description

Dose-limiting toxicities, adverse events, safety MRI assessments

Time Frame

1 month in DE phase, 3 months in DC phase

Secondary Outcome Measure Information:

Title

Pharmacodynamic assessments

Description

Serum and cellular immunological assays

Time Frame

1 month in DE phase, 3 months in DC phase

Title

MRI assessments

Description

Safety MRIs

Time Frame

1 month in DE phase, 3 months in DC phase

Title

Clinical status

Description

Neurological examination, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), Fatigue Severity Scale (FSS), Multiple Sclerosis Quality of Life (MSQLI).

Time Frame

3 months in DC phase

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alison Luckey

Organizational Affiliation

Primorus Clinical Trials

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Tim Anderson

Organizational Affiliation

Department of Medicine, University of Otago

Official's Role

Principal Investigator

Facility Information:

Facility Name

Primorus Clinical Trials, 40 Stewart Street

City

Christchurch

State/Province

Canterbury

ZIP/Postal Code

8011

Country

New Zealand

12. IPD Sharing Statement

Citations:

PubMed Identifier

29177070

Citation

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.

Results Reference

derived

PubMed Identifier

28607691

Citation

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.

Results Reference

derived

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Safety Study of an Immunomodulating Microparticle to Treat Progressive Multiple Sclerosis

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