Natalizumab Treatment of Progressive Multiple Sclerosis

Secondary Progressive Multiple Sclerosis Clinical Trial

— NAPMS  

Official title:

Natalizumab Treatment of Progressive Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01077466
• Other study ID #: NAPMS version 3.4
• Status: Completed
• Phase: Phase 2
• First received: February 26, 2010
• Last updated: February 15, 2012
• Start date: March 2010
• Est. completion date: January 2012

Study information

• Verified date: February 2012
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines AgencyDenmark: Ethics CommitteeDenmark: Danish Dataprotection Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 55 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Primary Progressive Multiple Sclerosis
• Sclerosis
• Secondary Progressive Multiple Sclerosis

Intervention

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

Locations

Country	Name	City	State
Denmark	Danish Multiple Sclerosis Center, Section 2082, Rigshospitalet	Copenhagen

Sponsors (5)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Biogen, Copenhagen University Hospital, Hvidovre, Signifikans ApS, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cerebrospinal fluid (CSF) osteopontin	The primary endpoint is change in CSF osteopontin from baseline to week 60.	Change from baseline to week 60	Yes
Secondary	Expanded disability status scale (EDSS)	Change in expanded disability status scale (EDSS)from baseline to week 60	Baseline to week 60	Yes
Secondary	Timed 25-foot Walk (T25FW)		Baseline to week 60	Yes
Secondary	Multiple Sclerosis Impairment Score (MSIS)		Baseline to week 60	Yes
Secondary	Multiple Sclerosis Functional Composite		Baseline to week 60	Yes
Secondary	Short Form 36 Health Survey (SF36)		Baseline to week 60	No
Secondary	CSF Neurofilament Heavy Chain	Change in neurofilament heavy chain in the cerebrospinal fluid	Baseline to week 60	Yes
Secondary	CSF Myelin Basic Protein	Change in myelin basic protein in CSF from baseline to week 60	Baseline to week 60	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	Diffusion transfer imaging (DTI)	Change in FA and ADC in lesions, GM and NAWM between baseline and week 60.	Baseline to week 60	Yes
Secondary	CSF cell count	Change in CSF cell count from baseline to week 60	Baseline to week 60	Yes
Secondary	Change in IgG-index		Baseline to week 60	No
Secondary	CSF nitrogen oxide metabolites		Baseline to week 60	No
Secondary	CSF-serum albumine concentration quotient		Baseline to week 60	No
Secondary	CSF CXCL13		Baseline to week 60	Yes
Secondary	Matrix metalloproteinase-9 (MMP-9)		Baseline to week 60	No
Secondary	New Gadolinium-enhancing lesions (GdEL)		Baseline to week 60	Yes
Secondary	Volume of lesions on T2-weighted MRI images		Baseline to week 60	Yes
Secondary	Number of new or enlarging lesions on T2-weighted MRI images		Baseline to week 60	Yes