Longitudinal Pharmacokinetic, Pharmacodynamic, Immunological, and Biochemical Sample Collection With MRI and Relapse Analysis of a Tysabri Patient Cohort
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 229
- 试验地点
- 1
- 主要终点
- Duration Effect of natalizumab
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Aged 18 to 80 years old, inclusive, 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 have participated in IIT I (Foley, IIT 1 001-001-TY) in March, April, or May of
- •Must have a magnetic resonance imaging (MRI) brain scan, performed prior to the initiation of treatment with natalizumab, on file.
- •Must weigh between 38 and 180 kg, inclusive.
- •Up to 40 patients will be asked to also participate in Part B, the PK/PD subset,
- •Approximately fifty patients will be asked to also participate in the sub-study Part C. These patients will have been in the bottom 20th percentile for iATP in Foley IIT 1 001-001-TY.
排除标准
- •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.
结局指标
主要结局
Duration Effect of natalizumab
时间窗: 18 months
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.
次要结局
- Stability of cell trafficking inhibition(18 months)
研究者
John F. Foley, MD
Sponsor-Ivestigator
Rocky Mountain MS Research Group, LLC