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弗里德赖希共济失调患者的 RTA 408 胶囊 - MOXIe

2026年8月13日 更新者：Biogen

RTA 408 治疗弗里德赖希共济失调 (MOXIe) 的安全性、有效性和药效学的 2 期研究

弗里德赖希共济失调是由三联体重复扩增引起的常染色体隐性遗传性小脑性共济失调。 致病突变是 frataxin 基因第一个内含子中的三核苷酸 (GAA) 重复扩增，导致 frataxin 的转录受损。 frataxin 缺乏的病理后果包括铁硫簇生物合成的严重破坏、线粒体铁过载与细胞铁失调相关，以及对氧化应激的敏感性增加。

弗里德赖希共济失调的一个标志是抗氧化防御机制受损，这在疾病进展中起着重要作用。 研究表明，弗里德赖希共济失调患者的核因子红细胞衍生 2 相关因子 2 (Nrf2) 信号严重受损。 因此，假设 omaveloxolone (RTA 408) 激活 Nrf2 和诱导抗氧化靶基因的能力对弗里德赖希共济失调患者具有治疗作用。

这项分为两部分的研究将评估 omaveloxolone (RTA 408) 在治疗弗里德赖希共济失调患者中的疗效、安全性和药效学。

第 1 部分：本研究的第一部分将是一项随机、安慰剂对照、双盲、剂量递增研究，以评估不同剂量的 omaveloxolone (RTA 408) 在 Friedreich 共济失调患者中的安全性。

第 2 部分：本研究的第二部分是一项随机、安慰剂对照、双盲、平行组研究，旨在评估 omaveloxolone (RTA 408) 150 mg 对弗里德赖希共济失调患者的安全性和有效性。 参加第 2 部分的患者将按照 1:1 的比例随机接受 omaveloxolone (RTA 408) 150 mg 或安慰剂。

扩展：扩展将评估 omaveloxolone (RTA 408) 在完成第 1 部分或第 2 部分后符合条件的弗里德赖希共济失调患者的长期安全性和耐受性。患者在进入第 1 部分或第 2 部分时将不会揭盲以研究第 1 部分或第 2 部分中的治疗扩展研究。 患者将每天一次接受 150 mg 的开放标签 omaveloxolone (RTA 408)。

研究概览

地位

完全的

条件

干预/治疗

详细说明

这项研究之前由 Reata Pharmaceuticals 发布。 2023 年 9 月，该试验的赞助权转移给百健 (Biogen)。

研究类型

介入性

注册 (实际的)

172

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 奥地利
      • Innsbruck、奥地利、6020
        • Medical University Innsbruck
  • 意大利
      • Milan、意大利、20133
        • Neurological Institute Carlo Besta
  • 澳大利亚
    • Victoria
      • Parkville、Victoria、澳大利亚、3052
        • Murdoch Childrens Research Institute
  • 美国
    • California
      • Los Angeles、California、美国、90095
        • UCLA
    • Florida
      • Gainesville、Florida、美国、32610
        • University of Florida - Neurology
      • Tampa、Florida、美国、33612
        • USF Ataxia Research Center
    • Georgia
      • Atlanta、Georgia、美国、30329
        • Emory University Hospital - Neurology
    • Iowa
      • Iowa City、Iowa、美国、52242
        • University of Iowa Stead Family Children's Hospital
    • Ohio
      • Columbus、Ohio、美国、43221
        • Ohio State University - Neurology
    • Pennsylvania
      • Philadelphia、Pennsylvania、美国、19104
        • Children's Hospital of Philadelphia
  • 英国
      • London、英国、WC1E 6BT
        • University College of London

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

16年 至 40年 (孩子、成人)

接受健康志愿者

不

描述

纳入标准：

  1. 从基因上证实了弗里德赖希的共济失调
  2. 修改后的 FARS 评分≥20 且≤80
  3. 年龄≥16岁且≤40岁的男性或女性
  4. 在研究第 1 天之前的 30 天内没有改变运动方案，并且愿意在 16 周的研究期间保持相同的运动方案
  5. 有能力完成最大运动测试
  6. 能够吞服胶囊

排除标准：

  1. 患有不受控制的糖尿病 (HbA1c >11.0%)
  2. B 型利钠肽值 >200 pg/mL
  3. 有有临床意义的左心疾病史和/或有临床意义的心脏病史
  4. 已知有活动性真菌、细菌和/或病毒感染，包括人类免疫缺陷病毒或肝炎病毒（乙型或丙型）
  5. 已知或怀疑滥用药物或酒精
  6. 有临床血液学或生物化学的临床显着异常，包括但不限于天冬氨酸氨基转移酶或丙氨酸氨基转移酶升高超过正常上限的 1.5 倍
  7. 有任何异常的实验室测试值或严重的预先存在的医疗状况，研究者认为这会使患者因研究入组而面临风险

  8. 在研究第 1 天之前的 7 天内服用过以下任何药物，或计划在参与研究期间服用任何这些药物：

    1. 细胞色素 P450 2C8 或 3A4 的敏感底物（例如瑞格列奈、咪达唑仑、西地那非）
    2. 细胞色素 P450 3A4 的中度或强抑制剂或诱导剂（例如，卡马西平、苯妥英钠、环丙沙星、葡萄柚汁）
    3. p-糖蛋白转运体的底物（例如安立生坦、地高辛）
  9. 在研究第 1 天之前的 30 天内参加过任何其他介入性临床研究
  10. 有可能妨碍遵守研究程序的能力的认知障碍
  11. 之前参加过 omaveloxolone (RTA 408) 的试验

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：双倍的

武器和干预

参与者组/臂
干预/治疗
实验性的：Part 1: Omaveloxolone 2.5 and 5 mg
Participants received omaveloxolone 2.5 mg, oral capsule, QD for 2 weeks, followed by 5 mg Omaveloxolone, oral capsule, QD for 10 weeks.
药品：Omaveloxolone 胶囊，2.5 毫克
其他名称：
  • RTA 408 胶囊 2.5 毫克
药品：Omaveloxolone 胶囊，5 毫克
其他名称：
  • RTA 408 粒胶囊，5 毫克
实验性的：Part 1: Omaveloxolone 10 mg
Participants received omaveloxolone 10 mg, oral capsule, QD for 12 weeks.
药品：Omaveloxolone 胶囊，10 毫克
其他名称：
  • RTA 408 粒胶囊，10 毫克
实验性的：Part 1: Omaveloxolone 20 mg
Participants received omaveloxolone 20 mg, oral capsule, QD for 12 weeks.
药品：Omaveloxolone 胶囊，20 毫克
其他名称：
  • RTA 408 粒胶囊，20 毫克
实验性的：Part 1: Omaveloxolone 40 mg
Participants received omaveloxolone 40 mg, oral capsule, QD for 12 weeks.
药品：Omaveloxolone 胶囊，40 毫克
其他名称：
  • RTA 408 粒胶囊，40 毫克
实验性的：Part 1: Omaveloxolone 80 mg
Participants received omaveloxolone 80 mg, oral capsule, QD for 12 weeks.
药品：Omaveloxolone 胶囊，80 毫克
其他名称：
  • RTA 408 粒胶囊，80 毫克
实验性的：Part 1: Omaveloxolone 160 mg
Participants received omaveloxolone 160 mg, oral capsule, QD for 12 weeks.
药品：Omaveloxolone 胶囊，160 毫克
其他名称：
  • RTA 408 粒胶囊，160 毫克
实验性的：Part 1: Omaveloxolone 300 mg
Participants received omaveloxolone 300 mg, oral capsule, QD for 12 weeks.
药品：Omaveloxolone 胶囊，300 毫克
其他名称：
  • RTA 408 粒胶囊，300 毫克
安慰剂比较：Part 1: Placebo
Participants received placebo, oral capsule, QD for 12 weeks.
药品：安慰剂
实验性的：Part 2: Omaveloxolone 150 mg
Participants received omaveloxolone 150 mg, oral capsule, QD for 48 weeks.
药品：Omaveloxolone 胶囊，150 毫克
其他名称：
  • RTA 408 粒胶囊，150 毫克
安慰剂比较：Part 2: Placebo
Participants received placebo, oral capsule, QD for 48 weeks.
药品：安慰剂
实验性的：OLE: Placebo/ Omaveloxolone
All eligible participants who had received either omaveloxone or placebo in Part 1 and eligible participants who received placebo in Part 2 received omaveloxone, 150 mg, oral capsule, QD, until the drug was available through commercial channels or alternate post-trial access mechanisms, or until participant withdrawal, whichever was sooner (up to approximately 370 weeks).
药品：Omaveloxolone 胶囊，150 毫克
其他名称：
  • RTA 408 粒胶囊，150 毫克
实验性的：OLE: Omaveloxolone/ Omaveloxolone
All eligible participants who had received omaveloxone in Part 2 continued to receive omaveloxolone, 150 mg, oral capsule, QD until the drug was available through commercial channels or alternate post-trial access mechanisms, or until participant withdrawal, whichever was sooner (up to approximately 370 weeks).
药品：Omaveloxolone 胶囊，150 毫克
其他名称：
  • RTA 408 粒胶囊，150 毫克

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Part 1: Change From Baseline in Peak Work During Maximal Exercise Testing at Week 12
大体时间：Baseline, Week 12
Cycle ergometry using a recumbent stationary bicycle was used to conduct maximal exercise testing and workload was increased incrementally. Peak work is defined as the workload at which participants reach maximal volition (defined as an inability to continue to exercise due to exhaustion). A positive change from baseline suggests an improvement.
Baseline, Week 12
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
大体时间：From first dose of study drug up to end of Part 1 of the study (up to Week 16)
An adverse event (AE) was any unfavorable and unintended sign (including any clinically significant abnormal laboratory test result), symptom, or disease temporally associated with the use of the study drug whether or not it is considered to be study drug related. An SAE was any untoward medical occurrence that at any dose resulted in death, in the view of the Investigator, placed the participant at immediate risk of death, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. TEAEs were defined as any AEs, regardless of relationship to study drug, that had an onset or worsened in severity on or after the first dose of study drug.
From first dose of study drug up to end of Part 1 of the study (up to Week 16)
Part 2: Change From Baseline in the Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 48
大体时间：Baseline, Week 48
The Friedreich Ataxia Rating Scale (FARS) is a neurological-exam-based rating scale with five sections: Bulbar (section A), Upper Limb Coordination (section B), Lower Limb Coordination (section C), Peripheral Nervous System (section D), and Upright Stability (section E). mFARS is the sum of sections A (score 0 to 11), B (score 0 to 36), C (score 0 to 16), and E (score 0 to 36). The minimum score is 0 and the maximum score is 99. A lower score indicates better neurological function.
Baseline, Week 48
Part 2: Number of Participants With TEAEs and TESAEs
大体时间：From first dose of study drug up to end of Part 2 of the study (up to Week 52)
An AE was any unfavorable and unintended sign (including any clinically significant abnormal laboratory test result), symptom, or disease temporally associated with the use of the study drug whether or not it is considered to be study drug related. An SAE was any untoward medical occurrence that at any dose resulted in death, in the view of the Investigator, placed the participant at immediate risk of death, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. TEAEs were defined as any AEs, regardless of relationship to study drug, that had an onset or worsened in severity on or after the first dose of study drug.
From first dose of study drug up to end of Part 2 of the study (up to Week 52)

次要结果测量

结果测量
措施说明
大体时间
Part 1: Change From Baseline in the mFARS at Week 12
大体时间：Baseline, Week 12
The FARS is a neurological-exam-based rating scale with five sections: Bulbar (section A), Upper Limb Coordination (section B), Lower Limb Coordination (section C), Peripheral Nervous System (section D), and Upright Stability (section E). mFARS is the sum of sections A (score 0 to 11), B (score 0 to 36), C (score 0 to 16), and E (score 0 to 36). The minimum score is 0 and the maximum score is 99. A lower score indicates better neurological function.
Baseline, Week 12
Part 2: Number of Participants With Patient Global Impression of Change (PGI-C)
大体时间：Week 48
The PGI-C is a 7-point scale that requires participants to assess how much their illness has improved or worsened relative to their baseline state at the beginning of the trial. Participants self-rated their perceived change by completing the following statement: "Since I began trial treatment, my overall status is:" 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Minimally worse, 6=Much worse and 7=Very much worse. Lower score indicates better improvement. The categories with at least one participant having a PGI-C score are reported.
Week 48
Part 2: Number of Participants With Clinical Global Impression of Change (CGI-C)
大体时间：Week 48
The CGIC scale is a 7 point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of an intervention. The CGIC was assessed by completing the following statement "Compared to the participant's condition at the start of the trial, this participant's overall status is", where 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. Lower score indicates better improvement. The categories with at least one participant having a CGIC score are reported.
Week 48
Part 2: Change From Baseline in Performance on a 9-Hole Peg Test (9-HPT) at Week 48
大体时间：Baseline, Week 48
The 9-HPT is a brief, standardized, quantitative test of upper extremity (arm and hand) function. Both the dominant and nondominant hands were tested twice (2 consecutive trials of the dominant hand, followed immediately by 2 consecutive trials of the nondominant hand). The participant picks up pegs 1 at a time (9 in total), using 1 hand only, and places them into holes on the board as quickly as possible, in any order until all holes are filled. Then, without pausing, the participant removes the pegs 1 at a time and returns them as quickly as possible. The times recorded for the two trials for each hand are averaged, and the reciprocal average value for each hand was used in analyses. Longer test times reflect more impairment on the participant's upper extremity function, thus a negative change from baseline suggests an improvement.
Baseline, Week 48
Part 2: Change From Baseline in Performance on a 25-Foot Timed Walk Test (T25-FWT) at Week 48
大体时间：Baseline, Week 48
The T25-FWT is a quantitative mobility and leg function performance test based on time (in seconds) to complete a 25-foot walk. Participants were instructed to attempt two T25-FWT trials at each visit. Both walk times were averaged, and the reciprocal average value was used in analyses. Longer test times reflect more impairment on the participant's ability to walk, thus a negative change from baseline suggests an improvement.
Baseline, Week 48
Part 2: Total Number of Falls
大体时间：Up to Week 48
A fall was defined as "the participant unintentionally coming to rest on the ground or at a lower level." The total number of falls before and after study drug administration has been reported.
Up to Week 48
Part 2: Change From Baseline in Peak Work During Maximal Exercise Testing at Week 48
大体时间：Baseline, Week 48
Cycle ergometry using a recumbent stationary bicycle was used to conduct maximal exercise testing and workload was increased incrementally. Peak work is defined as the workload at which participants reach maximal volition (defined as an inability to continue to exercise due to exhaustion). A positive change from baseline suggests an improvement.
Baseline, Week 48
Part 2: Change From Baseline in the Activities of Daily Living (ADL) Score at Week 48
大体时间：Baseline, Week 48
The ADL scale examines the ability of participants to complete everyday tasks (e.g., holding a fork, dressing). The ADL is a 9-question assessment, with the total score being the sum of 9 questions. The ADL survey assesses 9 concepts: (1) speech; (2) swallowing; (3) cutting food and handling utensils; (4) dressing; (5) personal hygiene; (6) falling; (7) walking; (8) quality of sitting position; and (9) bladder function. Each of these is rated on a 5-point scale where 0= normal and 4= severe disability/inability to carry out activity independently, for a total possible score of 0 to 36, with higher scores representing greater disability/dependency. A negative change from baseline indicates improvement.
Baseline, Week 48

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Biogen

合作者

AbbVie
Friedreich's Ataxia Research Alliance

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2015年1月31日

初级完成 (实际的)

2019年10月31日

研究完成 (实际的)

2025年12月19日

研究注册日期

首次提交

2014年9月30日

首先提交符合 QC 标准的

2014年9月30日

首次发布 (估计的)

2014年10月2日

研究记录更新

最后更新发布 (实际的)

2026年9月3日

上次提交的符合 QC 标准的更新

2026年8月13日

最后验证

2026年8月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • RTA 408-C-1402
  • 2024-517436-22 (其他标识符：EU CTIS Number)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

根据百健 (Biogen) 的临床试验透明度和数据共享政策 https://www.biogentrialtransparency.com/

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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