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

Alnylam Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Hereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy; hATTR-PN

Treatments: Drug: Vutrisiran; Drug: Nucresiran

Study type: Interventional

Funder types: Industry

Identifiers

NCT07223203

ALN-TTRSC04-004

2025-522544-40-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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

Enrollment: 125 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

125 participants in 2 patient groups

Nucresiran 300 mg

Experimental group

Description:

Patients will be administered nucresiran 300 mg subcutaneously (SC) once every 6 months (q6M) during the Treatment Period and Treatment Extension Period

Treatment:

Drug: Nucresiran

Vutrisiran 25 mg followed by Nucresiran 300 mg

Active Comparator group

Description:

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

Treatment:

Drug: Nucresiran

Drug: Vutrisiran