Longitudinal Pharmacokinetic, Pharmacodynamic, Immunological, and Biochemical
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis
Study type: Observational

Summary: 
      This is an open-label study of patients with relapsing forms of Multiple Sclerosis designed
      to assess the longitudinal pharmacokinetic, pharmacodynamic, immunological, and biochemical
      sample collection with MRI and relapse analysis of a Tysabri patient cohort. The study hopes
      to identify secondary and tertiary risk stratification markers that would aid in the clinical
      management of patients who are JC antibody positive.
    

Detailed description: 
      Progressive multifocal leukoencephalopathy (PML) has been related to the utilization of
      Tysabri as a therapeutic agent in the treatment of multiple sclerosis. The etiologic agent is
      the human polyomavirus JC. PML can result from lytic infection of glial cells via a mutant JC
      virus in multiple sclerosis patients being actively treated with Tysabri. The mutated JC
      virus is a neurotrophic virus that infects only humans. "The regulatory region sequence of
      the JC virus is hypervariable and contains determinants for neurotropism and neurovirulence."
      (Jensen and Major, 2001). In patients initially infected for the most part in childhood the
      virus tends to remain quiescent in kidneys, bone marrow and lymphoid tissue. The true
      incidence of JC virus seroprevalance is currently being assessed via two Biogen Idec clinical
      trials (STRATIFY 1 101JC401 and STRATIFY 2 101JC402). Application has been made to the FDA
      regarding a label change for Tysabri which will incorporate the use of the JC antibody assay.
      Upon FDA approval of the label change, the JC assay will serve as a primary risk
      stratification tool in the clinical use of Tysabri. Secondary and tertiary risk
      stratification markers would greatly aid in the clinical management of patients who are JC
      antibody positive.
    

Observational model: Case-Only
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with relapsing forms of MS. Conducted at one site in the US. Subjects currently
        enrolled in TOUCH Prescribing Program, and participated in Foley 001-001-TY eligible.

        Subset of approx. 40 patients to participate in Part B. 11 high risk bivalent patients 11
        low risk monovalent patients 9 patients who participated in 2009 PK/PD study (Biogen Idec,
        101MS406) 9 patients with infusion cycle of 38 days plus or minus 2 days

        Part C "Intracellular energetic in Tysabri therapy":

        Patients whose iATP fell into the bottom 20th percentile will be asked to participate in a
        sub-study that includes Part A with the addition of collecting iATP. This number is
        approximately 50 participants.

        Part D patients from 001-001-TY with low or normal IgG4 levels will be asked to participate
        in sub-study for an additional IgG4 assay collected at 3-5 days post-infusion. This number
        is approximately 30 participants.
      
Biospecimen description: 
      Serum for PK/PD, SVCAM back-up samples will be kept.
    
Keywords: Longitudinal assessment of biomarkers; duration of natalizumab; stratification of risk for PML