Natalizumab Treatment of Progressive Multiple Sclerosis (NAPMS)

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.

Study Overview

• Status: Completed
• Conditions: Primary Progressive Multiple Sclerosis; Secondary Progressive Multiple Sclerosis
• Intervention / Treatment: Drug: Natalizumab

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Danish Multiple Sclerosis Center, Section 2082, Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebrospinal fluid (CSF) osteopontin	The primary endpoint is change in CSF osteopontin from baseline to week 60.	Change from baseline to week 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expanded disability status scale (EDSS)	Change in expanded disability status scale (EDSS)from baseline to week 60	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	Change in neurofilament heavy chain in the cerebrospinal fluid	Baseline to week 60
CSF Myelin Basic Protein	Change in myelin basic protein in CSF from baseline to week 60	Baseline to week 60
Atrophy	Change in normalised brain volume (NBV), grey matter volume (GMV) og white matter volume (WMV) from week 12 to week 60	Week 12 to week 60
Magnetization transfer ratio (MTR)	Change in MTR in whole brain, lesions, normal-appearing grey matter (NAGM) og normal-appearing white matter (NAWM) from baseline to week 60	Baseline to week 60
Diffusion transfer imaging (DTI)	Change in FA and ADC in lesions, GM and NAWM between baseline and week 60.	Baseline to week 60
CSF cell count	Change in CSF cell count from baseline to week 60	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

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: University of Copenhagen; Biogen; Copenhagen University Hospital, Hvidovre; Signifikans ApS
• Investigators: Principal Investigator: Finn Sellebjerg, MD PhD DMSc, Danish Multiple Sclerosis Center

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: February 26, 2010
• First Submitted That Met QC Criteria: February 26, 2010
• First Posted (Estimate): March 1, 2010

Study Record Updates

• Last Update Posted (Estimate): February 17, 2012
• Last Update Submitted That Met QC Criteria: February 15, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Treatment; Safety; Efficacy; Cerebrospinal fluid; Natalizumab; Secondary Progressive Multiple Sclerosis; Primary Progressive Multiple Sclerosis; Osteopontin
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Physiological Effects of Drugs; Immunologic Factors; Natalizumab
• Other Study ID Numbers: NAPMS version 3.4