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
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Drug: Natalizumab
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Biomarkers Associated With Response to Natalizumab in Multiple Sclerosis Patients. A Prospective Multicentric Open Label Phase IV Study

Resource links provided by NLM:


Further study details as provided by University Hospital, Toulouse:

Primary Outcome Measures:
  • haplotypic frequency difference between responders and non-responders [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]

Enrollment: 300
Study Start Date: June 2009
Study Completion Date: March 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Natalizumab
    300mg, IV, every 4 weeks
    Other Name: Tysabry (brand name)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00942214

Locations
France
service de neurologie, hôpital Purpan
Toulouse, France, 31059
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
Principal Investigator: David Brassat, MD, PhD University Hospital, Toulouse
  More Information

No publications provided

Responsible Party: LESTIME Elodie, University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT00942214     History of Changes
Other Study ID Numbers: 0811001
Study First Received: July 16, 2009
Last Updated: March 29, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Toulouse:
Multiple sclerosis
natalizumab
pharmacogenomics

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
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 July 20, 2014