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

NCT07223203 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: ALN-TTRSC04-0042025-522544-40-00
• Study Type: interventional
• Target: 125
• Locations: 3 countries
• Sites: 4

Brief Summary

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

Conditions

hATTR-PN; Hereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy

Keywords

Polyneuropathy; Amyloidosis; Transthyretin; TTR; RNAi therapeutic

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and Month 9

Secondary Outcomes (10)

• 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

Study Arms (2)

Nucresiran 300 mg

EXPERIMENTAL

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

Drug: Nucresiran

Vutrisiran 25 mg followed by Nucresiran 300 mg

ACTIVE COMPARATOR

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

Drug: Nucresiran; Drug: Vutrisiran

Interventions

Nucresiran DRUG

Nucresiran 300 mg administered SC q6M

Also known as: ALN-TTRSC04

Nucresiran 300 mg; Vutrisiran 25 mg followed by Nucresiran 300 mg

Vutrisiran DRUG

Vutrisiran 25 mg administered SC q3M

Also known as: AMVUTTRA, ALN-TTRSC02

Vutrisiran 25 mg followed by Nucresiran 300 mg

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (4)

Clinical Trial Site

Boston, Massachusetts, 02118, United States

RECRUITING

Clinical Trial Site

Dallas, Texas, 75246, United States

NOT YET RECRUITING

Clinical Trial Site

Seoul, 06351, South Korea

NOT YET RECRUITING

Clinical Trial Site

Stockholm, 113 61, Sweden

NOT YET RECRUITING

MeSH Terms

Conditions

Polyneuropathies; Amyloidosis

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Medical Director

  Alnylam Pharmaceuticals Inc

  STUDY DIRECTOR

Central Study Contacts

Clinical Trial Information Line

CONTACT

1-877-ALNYLAM; clinicaltrials@alnylam.com

Clinical Trial Information Line

CONTACT

1-877-256-9526; clinicaltrials@alnylam.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2025
• First Posted: October 31, 2025
• Study Start: December 12, 2025
• Primary Completion (Estimated): December 27, 2027
• Study Completion (Estimated): June 12, 2031
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (2); SE (1); KR (1)