NAPMS: Natalizumab Treatment of Progressive Multiple Sclerosis

Sponsor

Rigshospitalet, Denmark (Other)

Overall Status

Completed

CT.gov ID

NCT01077466

Collaborator

Copenhagen University Hospital, Hvidovre (Other), Biogen (Industry), University of Copenhagen (Other), Signifikans ApS (Other)

Enrollment

Location

Arm

Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to study safety and efficacy of natalizumab treatment of primary and secondary progressive multiple sclerosis.

This will be done by measuring the effect of treatment on inflammation in the CNS by means of osteopontin levels in the cerebrospinal fluid (CSF). Safety measures further includes physical and neurological examination,blood samples and MRI measures of disease activity.

Condition or Disease	Intervention/Treatment	Phase
Primary Progressive Multiple Sclerosis Secondary Progressive Multiple Sclerosis	Drug: Natalizumab	Phase 2

Detailed Description

The study will include 12 secondary progressive multiple sclerosis patients and 12 primary progressive multiple sclerosis patients to treatment with IV natalizumab for 60 weeks. At baseline and week 60 a lumbar puncture will be performed. MRI scans will be performed at baseline week 12 and week 60.Safety blood samples will be collected every 12 week.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Natalizumab Treatment of Progressive Multiple Sclerosis

Study Start Date :

Mar 1, 2010

Actual Primary Completion Date :

Jan 1, 2012

Actual Study Completion Date :

Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Natalizumab 24 patients: 12 with secondary progressive multiple sclerosis 12 with primary progressive multiple sclerosis	Drug: Natalizumab 300 mg Natalizumab IV for every 4 week for 56 weeks (15 doses for every patient) Other Names: Tysabri

Arm

Intervention/Treatment

Experimental: Natalizumab

24 patients: 12 with secondary progressive multiple sclerosis 12 with primary progressive multiple sclerosis

Drug: Natalizumab

300 mg Natalizumab IV for every 4 week for 56 weeks (15 doses for every patient)

Other Names:

Tysabri

Outcome Measures

Primary Outcome Measures

Cerebrospinal fluid (CSF) osteopontin [Change from baseline to week 60]
The primary endpoint is change in CSF osteopontin from baseline to week 60.

Secondary Outcome Measures

Expanded disability status scale (EDSS) [Baseline to week 60]
Change in expanded disability status scale (EDSS)from baseline to week 60
Timed 25-foot Walk (T25FW) [Baseline to week 60]
Multiple Sclerosis Impairment Score (MSIS) [Baseline to week 60]
Multiple Sclerosis Functional Composite [Baseline to week 60]
Short Form 36 Health Survey (SF36) [Baseline to week 60]
CSF Neurofilament Heavy Chain [Baseline to week 60]
Change in neurofilament heavy chain in the cerebrospinal fluid
CSF Myelin Basic Protein [Baseline to week 60]
Change in myelin basic protein in CSF from baseline to week 60
Atrophy [Week 12 to week 60]
Change in normalised brain volume (NBV), grey matter volume (GMV) og white matter volume (WMV) from week 12 to week 60
Magnetization transfer ratio (MTR) [Baseline to week 60]
Change in MTR in whole brain, lesions, normal-appearing grey matter (NAGM) og normal-appearing white matter (NAWM) from baseline to week 60
Diffusion transfer imaging (DTI) [Baseline to week 60]
Change in FA and ADC in lesions, GM and NAWM between baseline and week 60.
CSF cell count [Baseline to week 60]
Change in CSF cell count from baseline to week 60
Change in IgG-index [Baseline to week 60]
CSF nitrogen oxide metabolites [Baseline to week 60]
CSF-serum albumine concentration quotient [Baseline to week 60]
CSF CXCL13 [Baseline to week 60]
Matrix metalloproteinase-9 (MMP-9) [Baseline to week 60]
New Gadolinium-enhancing lesions (GdEL) [Baseline to week 60]
Volume of lesions on T2-weighted MRI images [Baseline to week 60]
Number of new or enlarging lesions on T2-weighted MRI images [Baseline to week 60]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age between 19 and 55 years
Progressive disease course of multiple sclerosis (primary or secondary)
Duration of progressive phase of at least 1 year
Progression of > 1 EDSS point during the last 2 years (>½ EDSS point if EDSS > 5,5)
EDSS </= 6.5
Written and informed consent

Exclusion Criteria:

Pregnancy, breast-feeding or lack of anti.conception for fertile women.
Attack during the last month before inclusion.
Treatment with methylprednisolone during 3 months before inclusion.
Treatment with interferon-beta, glatirameracetate, immunoglobulin G or other immune-modulating treatment 3 months prior to inclusion.
Treatment with mitoxantrone, cyclophosphamide, azathioprine or other strong immunosuppressive drug 6 months prior to inclusion.
Prior experimental treatment with strong immunosuppressive drug which the treating physician means will influence the results of the trial.
Diseases associated with immunodeficiency.
Treatment with other anticoagulant than aspirin.
Current malign disease.
Diabetes Mellitus or other autoimmune disease.
Renal insufficiency or creatinine > 150 μmol/l.
Travel in tropical areas 3 months prior to inclusion.
Acute or chronic infectious diseases, which the treating physician finds relevant (e.g.hepatitis B virus, hepatitis C virus, HIV).
Psychiatric disease or other circumstances that may limit the patients participation in the trial.
Contraindication for MRI scan or gadolinium contrast .
Known hypersensitivity to natalizumab.