Natalizumab Treatment of Progressive Multiple Sclerosis - Full Text View

Sponsor:	Rigshospitalet, Denmark
Collaborators:	Copenhagen University Hospital, Hvidovre Biogen Idec University of Copenhagen Signifikans ApS
Information provided by (Responsible Party):	Finn Sellebjerg, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:	NCT01077466

Purpose

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	Intervention	Phase
Primary Progressive Multiple Sclerosis Secondary Progressive Multiple Sclerosis	Drug: Natalizumab	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Natalizumab Treatment of Progressive Multiple Sclerosis

Resource links provided by NLM:

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Natalizumab

U.S. FDA Resources

Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:

Cerebrospinal fluid (CSF) osteopontin [ Time Frame: Change from baseline to week 60 ] [ Designated as safety issue: Yes ]
The primary endpoint is change in CSF osteopontin from baseline to week 60.

Secondary Outcome Measures:

Expanded disability status scale (EDSS) [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: Yes ]
Change in expanded disability status scale (EDSS)from baseline to week 60
Timed 25-foot Walk (T25FW) [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: Yes ]
Multiple Sclerosis Impairment Score (MSIS) [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: Yes ]
Multiple Sclerosis Functional Composite [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: Yes ]
Short Form 36 Health Survey (SF36) [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: No ]
CSF Neurofilament Heavy Chain [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: Yes ]
Change in neurofilament heavy chain in the cerebrospinal fluid
CSF Myelin Basic Protein [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: Yes ]
Change in myelin basic protein in CSF from baseline to week 60
Atrophy [ Time Frame: Week 12 to week 60 ] [ Designated as safety issue: Yes ]
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) [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: Yes ]
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) [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: Yes ]
Change in FA and ADC in lesions, GM and NAWM between baseline and week 60.
CSF cell count [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: Yes ]
Change in CSF cell count from baseline to week 60
Change in IgG-index [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: No ]
CSF nitrogen oxide metabolites [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: No ]
CSF-serum albumine concentration quotient [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: No ]
CSF CXCL13 [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: Yes ]
Matrix metalloproteinase-9 (MMP-9) [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: No ]
New Gadolinium-enhancing lesions (GdEL) [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: Yes ]
Volume of lesions on T2-weighted MRI images [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: Yes ]
Number of new or enlarging lesions on T2-weighted MRI images [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: Yes ]

Enrollment:	24
Study Start Date:	March 2010
Study Completion Date:	January 2012
Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: Tysabri

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.

Eligibility

Ages Eligible for Study:	19 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01077466

Locations

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

Sponsors and Collaborators

Rigshospitalet, Denmark

Copenhagen University Hospital, Hvidovre

Biogen Idec

University of Copenhagen

Signifikans ApS

Investigators

Principal Investigator:

Finn Sellebjerg, MD PhD DMSc

Danish Multiple Sclerosis Center

More Information

No publications provided

Responsible Party:	Finn Sellebjerg, Assoc. professor, MD, PhD, DMSci, Finn Sellebjerg, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:	NCT01077466 History of Changes
Other Study ID Numbers:	NAPMS version 3.4
Study First Received:	February 26, 2010
Last Updated:	February 15, 2012
Health Authority:	Denmark: Danish Medicines Agency Denmark: Ethics Committee Denmark: Danish Dataprotection Agency

Keywords provided by Rigshospitalet, Denmark:

Primary Progressive Multiple Sclerosis
Secondary Progressive Multiple Sclerosis
Natalizumab
Treatment

Safety
Efficacy
Cerebrospinal fluid
Osteopontin

Additional relevant MeSH terms:

Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Chronic Progressive
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System

Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on May 24, 2012