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
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%
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)
Parallel
Nucresiran
DrugNucresiran 300 mg administered SC q6M
Vutrisiran
DrugVutrisiran 25 mg administered SC q3M
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
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.
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
The Norfolk QoL-DN is a standardized 35-item patient-rated questionnaire used to assess 5 domains: physical function, large fiber neuropathy, activities of daily living, symptoms, small fiber neuropathy, and autonomic neuropathy. The minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome.
Percent Reduction in Serum TTR Levels in the Nucresiran Group Compared to the In-study Vutrisiran Group through 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
The mBMI, which is a measure of nutritional status, is calculated as the product of body mass index (BMI) (weight in kilograms divided by the square of height in meters) and serum albumin (g/L) to reflect fluid balance, such as fluid accumulation or dehydration. A negative change from baseline indicates a better outcome.
Change from Baseline in the mNIS+7 Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18
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.
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