An Open Label Study to Assess the Pharmacokinetic Profile of Nusinersen (BIIB058) Administered Via the ThecaFlex DRx™ System (PIERRE-PK)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Biogen
- 入组人数
- 78
- 试验地点
- 34
- 主要终点
- Maximum Observed Concentration (Cmax) of Nusinersen Delivered via Standard LP and via ThecaFlex DRx System
研究概览
简要总结
In this PIERRE-PK study, researchers will learn how the body processes nusinersen when it is given through the ThecaFlex DRx™ System, compared to when nusinersen is given by lumbar puncture (LP). The ThecaFlex DRx system is an investigational implantable medical device developed by Alcyone Therapeutics, Inc. It consists of a catheter, which is a flexible tube, connected to a port which is placed under the skin. Alcyone Therapeutics, Inc. has an ongoing study called PIERRE to test the ThecaFlex DRx system. Participants with spinal muscular atrophy (SMA) in the PIERRE study may be enrolled in the PIERRE-PK study.
The main goal of the PIERRE-PK study is to learn how the body processes nusinersen when given by the ThecaFlex DRx system compared to a lumbar puncture. The main questions researchers want to answer are:
- What is the highest amount of nusinersen found in the blood after dosing?
- How much nusinersen is found in the blood over the first 24 hours after dosing?
The PIERRE-PK study will be done as follows:
- Participants will be screened to check if they can join the study. The screening period will be up to 30 days for this study and may overlap with the PIERRE study.
- Participants will join 1 of 2 groups based on their ongoing nusinersen treatment. One group will be receiving 12 mg doses of nusinersen. The other group will be receiving 28 mg doses of nusinersen.
- Participants will first receive a dose of nusinersen by lumbar puncture.
- The ThecaFlex DRx system will be implanted after the lumbar puncture, as part of the PIERRE study.
- Participants will receive a dose of nusinersen by the ThecaFlex DRx system, as part of the PIERRE study. This dose will be a regular maintenance dose that happens about 4 months after their first dose in this study.
- Researchers will take blood samples before and after each dose. The last blood sample will be taken 24 hours after the dose.
- The total study duration for each participant in the PIERRE-PK study will be approximately 5 months. This period will overlap with the participant's first 5 months in the PIERRE study.
详细描述
The primary objective of this study is to assess the Pharmacokinetic (PK) profile of nusinersen delivered via standard LP and via the ThecaFlex DRx System in participants with SMA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Participants must be screened in the PIERRE study to be eligible for enrollment in the PIERRE PK study.
- •Participants in the 12 mg group
- •Participant must have completed all 4 required 12 mg loading doses as per the approved 12 mg dose regimen.
- •Participant is on regular LP maintenance dosing of nusinersen 12 mg every 4 months, with 120 days ± 14 days between the LP-delivered study dose and the last nusinersen dose prior to study enrollment.
- •Participants in the 28 mg group
- •Participant must have completed 1 or 2 of the 50 mg loading doses as per the approved 50/28 mg dose regimen.
- •Participant is on regular LP maintenance dosing of nusinersen 28 mg every 4 months, with 120 days ± 14 days between the LP-delivered study dose and the last nusinersen dose prior to study enrollment.
排除标准
- •Ongoing participation or participation within 6 months or 5 half-lives of the agent (whichever is longer) of enrollment in other interventional clinical trials for the treatment of SMA (except for the PIERRE study or interventional clinical trials of myostatin inhibitors [e.g., apitegromab and taldefgrobep alfa]).
- •Participant is naïve to nusinersen treatment.
- •Participant is receiving nusinersen at a dose other than 12 mg or 28 mg.
- •Participant has already undergone implantation of the ThecaFlex DRx system or any other implantable medical device for intrathecal (IT) administration.
- •Participant is pregnant, currently breastfeeding, or intending to become pregnant during the study.
- •NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Nusinersen Via LP and ThecaFlex DRx System
Participants will receive a maintenance dose of nusinersen, 12 milligrams (mg) via LP in the PIERRE-PK study, followed by implantation of the ThecaFlex DRx System and the subsequent nusinersen 12 mg maintenance dose via the system in the PIERRE study.
干预措施: Nusinersen (Drug)
Nusinersen Via LP and ThecaFlex DRx System
Participants will receive a maintenance dose of nusinersen, 12 milligrams (mg) via LP in the PIERRE-PK study, followed by implantation of the ThecaFlex DRx System and the subsequent nusinersen 12 mg maintenance dose via the system in the PIERRE study.
干预措施: ThecaFlex DRx System (Device)
Nusinersen 28 mg Via LP and ThecaFlex DRx System
Participants will receive a maintenance dose of nusinersen, 28 mg via LP in the PIERRE-PK study, followed by implantation of the ThecaFlex DRx System and the subsequent nusinersen 28 mg maintenance dose via the system in the PIERRE study.
干预措施: ThecaFlex DRx System (Device)
Nusinersen 28 mg Via LP and ThecaFlex DRx System
Participants will receive a maintenance dose of nusinersen, 28 mg via LP in the PIERRE-PK study, followed by implantation of the ThecaFlex DRx System and the subsequent nusinersen 28 mg maintenance dose via the system in the PIERRE study.
干预措施: Nusinersen (Drug)
Nusinersen 12 mg Via LP and ThecaFlex DRx System
Participants will receive a maintenance dose of nusinersen, 12 milligrams (mg) via LP in the PIERRE-PK study, followed by implantation of the ThecaFlex DRx System and the subsequent nusinersen 12 mg maintenance dose via the system in the PIERRE study.
干预措施: ThecaFlex DRx System (Device)
Nusinersen 12 mg Via LP and ThecaFlex DRx System
Participants will receive a maintenance dose of nusinersen, 12 milligrams (mg) via LP in the PIERRE-PK study, followed by implantation of the ThecaFlex DRx System and the subsequent nusinersen 12 mg maintenance dose via the system in the PIERRE study.
干预措施: Nusinersen (Drug)
结局指标
主要结局
Maximum Observed Concentration (Cmax) of Nusinersen Delivered via Standard LP and via ThecaFlex DRx System
时间窗: Pre-dose and at multiple time points post-dose over 4 months
Area Under the Plasma Concentration-Time Curve From Zero Time to 24 Hours After Intrathecal Administration (AUC0-24h) of Nusinersen Delivered via Standard LP and via ThecaFlex DRx System
时间窗: Pre-dose and at multiple time points post-dose over 4 months
Maximum Observed Concentration (Cmax) of Nusinersen Delivered via Standard LP and via ThecaFlex DRx System
时间窗: Pre-dose and at multiple time points post-dose up to 4 months
Area Under the Plasma Concentration-Time Curve From Zero Time to 24 Hours After Intrathecal Administration (AUC0-24h) of Nusinersen Delivered via Standard LP and via ThecaFlex DRx System
时间窗: Pre-dose and at multiple time points post-dose up to 4 months
次要结局
未报告次要终点