Natalizumab Treatment of Progressive Multiple Sclerosis

Phase 2

Completed

• Conditions: Primary Progressive Multiple Sclerosis; Secondary Progressive Multiple Sclerosis
• Interventions: Drug: Natalizumab

• Registration Number: NCT01077466
• Lead Sponsor: Rigshospitalet, Denmark

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.

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 Timeline

• Study First Submitted: 2010-02-26
• Study First Submitted QC: 2010-02-26
• Study Start: 2010-03
• Study First Posted: 2010-03-01
• Primary Completion: 2012-01
• Study Completion: 2012-01
• Status Verified: 2012-02
• Last Update Submitted: 2012-02-15
• Last Update Posted: 2012-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Natalizumab	Natalizumab	24 patients: 12 with secondary progressive multiple sclerosis 12 with primary progressive multiple sclerosis

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Danish Multiple Sclerosis Center, Section 2082, Rigshospitalet; 🇩🇰 Copenhagen, Denmark