NCT04048577

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

The Impact of a Planned 12-week Dosing Interruption of Natalizumab on Immune Cell Trafficking, Pharmacokinetic (PK)/Pharmacodynamic (PD) Parameters, and Multiple Sclerosis (MS) Disease Stability.

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Berkovich, Regina MD, PhD Inc. · Academic / Other
• Sex: All
• Age: 21 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label study of patients with relapsing forms of MS is designed to assess the biochemical, immunological, and kinetic profiles of natalizumab being used with specific brief dosing interruption. The study will be conducted at one site in the US. Ten subjects currently treated with natalizumab will be enrolled and will be evaluated for both PK/PD and cell trafficking in blood and/or CSF during standard dosing of natalizumab and at the end of a planned 12-week dosing interruption. MS disease activity will be carefully monitored clinically and by MRI and NfL.

Detailed description

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.

Conditions

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting

Interventions

Type	Name	Description
DRUG	Dosing Interruption of Natalizumab	Planned 12 week dosing interruption of natalizumab

Timeline

• Start date: 2019-07-03
• Primary completion: 2021-11-01
• Completion: 2021-12-01
• First posted: 2019-08-07
• Last updated: 2021-07-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study