Biomarkers and Response to Natalizumab for Multiple Sclerosis Treatment (Bionat2)

This study has been completed.
Sponsor:
Information provided by:
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT00942214
First received: July 16, 2009
Last updated: March 29, 2011
Last verified: March 2011

July 16, 2009
March 29, 2011
June 2009
February 2011   (final data collection date for primary outcome measure)
haplotypic frequency difference between responders and non-responders [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00942214 on ClinicalTrials.gov Archive Site
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Biomarkers and Response to Natalizumab for Multiple Sclerosis Treatment
Biomarkers Associated With Response to Natalizumab in Multiple Sclerosis Patients. A Prospective Multicentric Open Label Phase IV Study

Information from blood samples may help us for choosing the best treatment in future personalized medicine. Natalizumab (NTZ) a current treatment for MS can be used as a second line therapy if a suboptimal response to disease modifying drugs. When to introduce NTZ is not consensual. The investigators hypothesized that biological information could rationalize choice and thus designed a prospective open label trial to test biological markers before treatment.

Current state of knowledge of the topic of the project and The general interest of the project; Pharmacogenomic aims to determine biomarkers related to treatment response, a step toward patient-tailored medicine. Natalizumab, a monoclonal antibody has just received the EMEA approval for MS patients who do not respond to interferon treatment or who experience a severe disease course. Efficacy of the drug is outstanding with 37% of the patients completing the "disease free" definition after 2 years (7% in placebo group). On the other hand, natalizumab may be associated with severe adverse events such as progressive multifocal leucoencephalopathy and high costs. Overall, this emphasizes the need beyond current approval criteria to identify those patients with the best efficacy to safety ratio, a major public health issue.

Scientific aims The primary scientific aim is to define biomarkers that would allow predicting long term response to natalizumab.

Methodology; The investigators plan to conduct a 5 years study to search for the best predicting factors at the beginning of treatment and after 2 years. In this grant application the investigators will perform a multivariate analysis of clinical, MRI, and biological markers (neutralizing antibody, DNA, and mRNA expression) from baseline to 2 years. For feasibility reasons, long term follow up (5 years) and proteomics study will be performed in a second stage.

Interventional
Phase 4
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Multiple Sclerosis
Drug: Natalizumab
300mg, IV, every 4 weeks
Other Name: Tysabry (brand name)
Not Provided
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
300
March 2011
February 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients between the ages of 18 and 55 years.
  • Diagnosis of relapsing multiple sclerosis according to McDonald criteria.
  • EDSS score of 0 to 5.0 on the EDSS scale. One of the following 2 items:

    1. Patients who have failed to respond to a full and adequate course of a beta-interferon. Patients have had at least 1 relapse in the previous year while on therapy, and have at least 9 T2-hyperintense lesions in cranial MRI or at least 1 Gadolinium-enhancing lesion.
    2. Patients with rapidly evolving severe relapsing remitting multiple sclerosis, defined by 2 or more disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI.

Exclusion Criteria:

  • Hypersensitivity to natalizumab or to any of the excipients.
  • Progressive Multifocal Leukoencephalopathy (PML).
  • Increased risk of opportunistic infections, including immunocompromised patients (including those currently receiving immunosuppressive therapies or those immunocompromised by prior therapies, e.g. mitoxantrone or cyclophosphamide within 1 year before Tysabri.
  • Combination with beta-interferons or glatiramer acetate.
  • Known active malignancies, except for patients with cutaneous basal cell carcinoma.
  • Children and adolescents.
Both
18 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00942214
0811001
No
LESTIME Elodie, University Hospital, Toulouse
University Hospital, Toulouse
Not Provided
Principal Investigator: David Brassat, MD, PhD University Hospital, Toulouse
University Hospital, Toulouse
March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP