A Pilot Study to Characterize the Biological Effect of a Pre-planned 12 Week Dose Interruption of Natalizumab

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Study Title: The impact of a planned 12-week dosing interruption of natalizumab on immune cell trafficking, PK/PD parameters, and MS disease stability. Objectives: Hypothesis: An interruption in the dosing of natalizumab results in a lower risk of progressive multifocal leukoencephalopathy (PML) whi...

Study Title: The impact of a planned 12-week dosing interruption of natalizumab on immune cell trafficking, PK/PD parameters, and MS disease stability. Objectives: Hypothesis: An interruption in the dosing of natalizumab results in a lower risk of progressive multifocal leukoencephalopathy (PML) while maintaining MS disease control by selective immune surveillance. Primary endpoints: To measure the re-establishment of immune surveillance by measuring leukocyte cell binding to the blood brain barrier and trafficking into the central nervous system (CNS) during a planned 12-week dosing interruption of natalizumab. This will be done by measuring leukocytes in the CSF. Concurrently, MS disease activity will be monitoring with MRI. Secondary endpoints: To characterize the difference in PK/PD parameters in patients during standard 28-day dosing intervals vs. at the end of a planned 12-week dosing interruption To measure natalizumab drug concentrations, Soluble Vascular Cell Adhesion Molecule (sVCAM), Soluble Mucosal Vascular Addressin Cell Adhesion Molecule (sMAdCAM), Very Late Antigen-4 (VLA4) expression, and receptor occupancy measured in blood. To measure neurofilament light (NfL) in CSF and serum as a sensitive measure of MS disease stability. Using MRI and clinical parameters, to determine impact of a planned 12-week dosing interruption of natalizumab on MS disease stability. MRI's will be obtained for each patient at the end of the dose interruption and 3 months after the re-initiation of natalizumab dosing. Design: Single site, open-label, consenting patients with relapsing forms of Multiple Sclerosis who are scheduled for a dose interruption of natalizumab. Patients will provide biological samples (blood and CSF) and have MRIs post-dose interruption. Patient Population: Patients with relapsing forms of Multiple Sclerosis who are currently on natalizumab therapy with stable MS disease and who are scheduled for a planned 12-week dosing interruption. Treatment Groups: Duration of Study Participation: Up to 9 months Study Location: 8727 Beverly Blvd, West Hollywood, California (CA) 90048 United States (US) Study Phase: Pilot exploratory study. Number of Planned Subjects: 10 Sample Size Determination: This is an exploratory study. No formal sample size calculation was performed.

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