TRITON-PN: A Phase 3, Global, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy (hATTR-PN)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 125
- 试验地点
- 60
- 主要终点
- Change from Baseline in the Modified Neuropathy Impairment Score +7 (mNIS+7) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 9
研究概览
简要总结
The purpose of this study is to:
- Determine the efficacy of nucresiran in patients with hATTR-PN by evaluating the effect on neurologic impairment, quality of life, nutritional status, disability, and gait speed
- Demonstrate superiority of nucresiran compared to in-study vutrisiran with respect to serum transthyretin (TTR) levels
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has documented diagnosis of hATTR-PN
- •Has a diagnosis of hATTR amyloidosis with polyneuropathy with a documented TTR gene variant
- •Has a neuropathy impairment score (NIS) of 5 to 130 (inclusive)
- •Has a Karnofsky Performance Status (KPS) of ≥60%
排除标准
- •Has had a liver transplant or is likely, in the opinion of the Investigator, to undergo liver transplantation during the Treatment Period of the study
- •Has known other (non-hATTR) forms of amyloidosis or clinical evidence of leptomeningeal amyloidosis
- •Has a New York Heart Association (NYHA) heart failure classification >2
- •Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 upper limit of normal (ULN)
- •Has total bilirubin >1.5 ULN
- •Has estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73m^2
- •Has other known causes of sensorimotor or autonomic neuropathy
研究组 & 干预措施
Vutrisiran 25 mg followed by Nucresiran 300 mg
Patients will be administered vutrisiran 25 mg SC every 3 months (q3M) during the Treatment Period followed by nucresiran 300 mg SC q6M during the Treatment Extension Period
干预措施: Nucresiran (Drug)
Nucresiran 300 mg
Patients will be administered nucresiran 300 mg subcutaneously (SC) once every 6 months (q6M) during the Treatment Period and Treatment Extension Period
干预措施: Nucresiran (Drug)
Vutrisiran 25 mg followed by Nucresiran 300 mg
Patients will be administered vutrisiran 25 mg SC every 3 months (q3M) during the Treatment Period followed by nucresiran 300 mg SC q6M during the Treatment Extension Period
干预措施: Vutrisiran (Drug)
结局指标
主要结局
Change from Baseline in the Modified Neuropathy Impairment Score +7 (mNIS+7) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 9
时间窗: Baseline and Month 9
The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness and deep tendon reflexes, electrophysiologic measurement of large nerve fiber function, sensory testing and postural blood pressure. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome.
次要结局
- Change from Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 9(Baseline and Month 9)
- Percent Reduction in Serum TTR Levels in the Nucresiran Group Compared to the In-study Vutrisiran Group through Month 9(Up to Month 9)
- Change from Baseline in Modified Body Mass Index (mBMI) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 9(Baseline and Month 9)
- Change from Baseline in the mNIS+7 Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18(Baseline and Month 18)
- Change from Baseline in Norfolk QoL-DN Total Score Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18(Baseline and Month 18)
- Change from Baseline in mBMI Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18(Baseline and Month 18)
- Change from Baseline in Rasch-built Overall Disability Scale (R-ODS) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18(Baseline and Month 18)
- Change from Baseline in Timed 10-meter Walk Test (10-MWT) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18(Baseline and Month 18)
- Percent Reduction in Serum TTR Levels in the Nucresiran Group Compared to the In-study Vutrisiran Group through Month 18(Up to Month 18)
- Percent Reduction in Serum TTR Levels in the Nucresiran Group Compared to the In-study Vutrisiran Group at Week 6(Week 6)