Longitudinal Pharmacokinetic, Pharmacodynamic, Immunological, and Biochemical
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.
|Study Design:||Observational Model: Case-Only
Time Perspective: Retrospective
|Official Title:||Longitudinal Pharmacokinetic, Pharmacodynamic, Immunological, and Biochemical Sample Collection With MRI and Relapse Analysis of a Tysabri Patient Cohort|
- Duration Effect of natalizumab [ Time Frame: 18 months ] [ Designated as safety issue: No ]Primary: To further understand the duration effect of natalizumab at the biochemical, cellular, and pharmacokinetic levels in natalizumab patients; identify biomarkers which could aid in patient risk modification for (PML). Assess the stability of natalizumab concentration via pharmacokinetic measurement in ug/ml.
- Stability of cell trafficking inhibition [ Time Frame: 18 months ] [ Designated as safety issue: No ]Secondary endpoint: Assess the stability of cell trafficking inhibition produced through steady state Natalizumab administration through an infusion cycle. Cell trafficking is measured via sVCAM, measurement units ng/mL.
Biospecimen Retention: Samples Without DNA
Serum for PK/PD, SVCAM back-up samples will be kept.
|Study Start Date:||April 2011|
|Study Completion Date:||August 2011|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
Tysabri (natalizumab) infusing
Patients with relapsing forms of MS who participated in 001-001-TY and are currently still infusing with Tysabri (natalizumab).
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01330498
|United States, Utah|
|Rocky Mountain Multiple Sclerosis Clinic|
|Salt Lake City, Utah, United States, 84103|
|Principal Investigator:||John F Foley, MD||Rocky Mountain MS Research Group, LLC|