TRITON-PN: A Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy

Phase 3RecruitingNCT07223203

Alnylam Pharmaceuticals125 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

125

Conditions

Hereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy hATTR-PN

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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% Exclusion Criteria: * 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

Outcomes

Primary Outcomes

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.

Time frame: Baseline and Month 9

Secondary Outcomes

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.

Time frame: Baseline and Month 9

Percent Reduction in Serum TTR Levels in the Nucresiran Group Compared to the In-study Vutrisiran Group through Month 9

Time frame: 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

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.

Time frame: 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