A Pilot Study to Characterize the Biological Effect of a Pre-planned 12 Week Dose Interruption of Natalizumab
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|ClinicalTrials.gov Identifier: NCT04048577|
Recruitment Status : Recruiting
First Posted : August 7, 2019
Last Update Posted : July 27, 2020
|Condition or disease||Intervention/treatment||Phase|
|Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting||Drug: Dosing Interruption of Natalizumab||Phase 4|
The impact of a planned 12-week dosing interruption of natalizumab on immune cell trafficking, PK/PD parameters, and MS disease stability.
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.
- 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.
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.
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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.|
|Actual Study Start Date :||July 3, 2019|
|Estimated Primary Completion Date :||February 1, 2021|
|Estimated Study Completion Date :||March 1, 2021|
Experimental: Dose Interruption
All subjects will continue to receive their prescribed Tysabri® 300 mg IV infusions at their approved infusion sites. The patients will receive Tysabri at standard intervals (28-days) except during the pre-planned dose interruption of 2 consecutive skipped doses.
Drug: Dosing Interruption of Natalizumab
Planned 12 week dosing interruption of natalizumab
Other Name: Dosing Interruption of Tysabri
No Intervention: Standard Treatment
All subjects will continue to receive their prescribed Tysabri® 300 mg IV infusions at their approved infusion sites. The patients will receive Tysabri at standard intervals (28-days).
- Leukocyte Type and Quantity in CSF [ Time Frame: Change of Leukocyte types and quantity in CSF in pre- and post-interruption of treatment through study completion, an average of 6 months. ]Types and quantities of leukocytes including T-cells, B-cells, macrophages, monocytes, etc. measured through flow cytometry.
- MS Activity through CSF, Blood, and MRI [ Time Frame: Change of MS Activity in pre- and post-interruption of treatment through study completion, an average of 6 months. ]Soluble factors related to MS activity include Neurofilament Light Chain Levels in Blood and CSF measured through flow cytometry. MRI of brain, cervical, and thoracic cavity will be closely monitored for MS disease activity.
- Natalizumab Concentrations in Blood [ Time Frame: Change of Natalizumab Concentrations in Blood in pre- and post-interruption of treatment through study completion, an average of 6 months. ]
- immunoglobulin G4 Levels in Blood [ Time Frame: Change of immunoglobulin G4 Levels in Blood in pre- and post-interruption of treatment through study completion, an average of 6 months. ]
- Soluble Vascular Cell Adhesion Molecules and Soluble Mucosal Vascular Addressin Cell Adhesion Molecule Levels (sVCAM sMAdCAM) in Blood [ Time Frame: Change of sVCAM sMAdCAM in blood in pre- and post-interruption of treatment through study completion, an average of 6 months. ]sVCAM sMAdCAM are ligands that are released into the bloodstream as marker of inflammation. The measurements will be done with Luminex technology using VCAM1 and MAdCAM1 specific antibodies to measure the levels in serum.
- John Cunningham Virus Extracellular Vesicle Antibody Levels in CSF [ Time Frame: Change of John Cunningham Virus Extracellular Vesicles in CSF in pre- and post-interruption of treatment through study completion, an average of 6 months. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04048577
|Contact: Regina R Berkovich, MD, PhDfirstname.lastname@example.org|
|United States, California|
|Regina Berkovich MD, PhD Inc.||Recruiting|
|West Hollywood, California, United States, 90048|
|Contact: Michael W Fernandez, BS 310-474-9595 email@example.com|
|Principal Investigator:||Regina R Berkovich, MD, PhD||Regina Berkovich MD, PhD Inc.|