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.
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Leukocyte Type and Quantity in CSF
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible for entry into this study, candidates must meet all of the following eligibility criteria at the time of randomization:
- •Screening Visit:
- •Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
- •At least 18 years old at the time of informed consent.
- •Must be a patient with a relapsing form of Multiple Sclerosis enrolled in the TOUCH Prescribing Program who is not expected to discontinue Tysabri® therapy prior to completion of the requirements of this study.
- •Must weigh between 50 and 110 kg, inclusive.
- •Patients must be considered clinically stable and scheduled for their pre-planned annual dose interruption of 2 consecutive skipped doses.
- •No evidence of disease activity with on standard (28-day interval) dosing of natalizumab.
排除标准
- •Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of screening:
- •Medical History
- •If subject answers 'Yes" to any question on the PML questionnaire that is not resolved prior to infusion as per standard operating procedure for natalizumab infusion.
- •If subject consumes alcohol within 24 hours of blood specimen collection.
研究组 & 干预措施
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.
干预措施: Dosing Interruption of Natalizumab (Drug)
结局指标
主要结局
Leukocyte Type and Quantity in CSF
时间窗: 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
时间窗: 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.
次要结局
- Natalizumab Concentrations in Blood(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(Change of immunoglobulin G4 Levels in Blood in pre- and post-interruption of treatment through study completion, an average of 6 months.)
- John Cunningham Virus Extracellular Vesicle Antibody Levels in CSF(Change of John Cunningham Virus Extracellular Vesicles in CSF 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(Change of sVCAM sMAdCAM in blood in pre- and post-interruption of treatment through study completion, an average of 6 months.)
研究者
Regina Radner Berkovich
Director
Berkovich, Regina MD, PhD Inc.