TRITON-PN: A Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy
TRITON-PN
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)
2 other identifiers
interventional
125
16 countries
41
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Dec 2025
Longer than P75 for phase_3
41 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 29, 2025
CompletedFirst Posted
Study publicly available on registry
October 31, 2025
CompletedStudy Start
First participant enrolled
December 12, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 27, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 12, 2031
July 23, 2026
July 1, 2026
2 years
October 29, 2025
July 22, 2026
Conditions
Keywords
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
- +5 more secondary outcomes
Study Arms (2)
Nucresiran 300 mg
EXPERIMENTALPatients will be administered nucresiran 300 mg subcutaneously (SC) once every 6 months (q6M) during the Treatment Period and Treatment Extension Period
Vutrisiran 25 mg followed by Nucresiran 300 mg
ACTIVE COMPARATORPatients 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
Interventions
Nucresiran 300 mg administered SC q6M
Vutrisiran 25 mg administered SC q3M
Eligibility Criteria
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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (41)
Clinical Trial Site
Aurora, Colorado, 80045, United States
Clinical Trial Site
Chicago, Illinois, 60611, United States
Clinical Trial Site
Baltimore, Maryland, 21287, United States
Clinical Trial Site
Boston, Massachusetts, 02118, United States
Clinical Trial Site
Rochester, Minnesota, 55905, United States
Clinical Trial Site
New York, New York, 10032, United States
Clinical Trial Site
Chapel Hill, North Carolina, 27514, United States
Clinical Trial Site
Dallas, Texas, 75246, United States
Clinical Trial Site
Houston, Texas, 77030, United States
Clinical Trial Site
Darlinghurst, 2010, Australia
Clinical Trial Site
Woolloongabba, 4102, Australia
Clinical Trial Site
Ribeirão Preto, 14051-140, Brazil
Clinical Trial Site
São Paulo, 04038-002, Brazil
Clinical Trial Site
Égkomi, 2371, Cyprus
Clinical Trial Site
Créteil, 94000, France
Clinical Trial Site
Le Kremlin-Bicêtre, 94270, France
Clinical Trial Site
Marseille, 13005, France
Clinical Trial Site
Berlin, 10117, Germany
Clinical Trial Site
Münster, 48149, Germany
Clinical Trial Site
Athens, 115 28, Greece
Clinical Trial Site
Heraklion, 715 00, Greece
Clinical Trial Site
Florence, 50134, Italy
Clinical Trial Site
Milan, 20133, Italy
Clinical Trial Site
Pavia, 27100, Italy
Clinical Trial Site
Roma, 00168, Italy
Clinical Trial Site
Kumamoto, 860-8556, Japan
Clinical Trial Site
Suita, 565-0871, Japan
Clinical Trial Site
Kuala Lumpur, 59100, Malaysia
Clinical Trial Site
Lisbon, 1649-035, Portugal
Clinical Trial Site
Porto, 4099-001, Portugal
Clinical Trial Site
Seoul, 05030, South Korea
Clinical Trial Site
Seoul, 06351, South Korea
Clinical Trial Site
Barcelona, 08035, Spain
Clinical Trial Site
Huelva, 21005, Spain
Clinical Trial Site
L'Hospitalet de Llobregat, 8907, Spain
Clinical Trial Site
Stockholm, 113 61, Sweden
Clinical Trial Site
Umeå, 907 37, Sweden
Clinical Trial Site
Taipei, 10002, Taiwan
Clinical Trial Site
Taipei, 112, Taiwan
Clinical Trial Site
Taoyuan City, 333, Taiwan
Clinical Trial Site
Istanbul, 34093, Turkey (Türkiye)
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Alnylam Pharmaceuticals
Central Study Contacts
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
July 23, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will share
Phase 2-4 trials: Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Access to data may be declined where there is likelihood a patient could be identified or other feasibility issue, where there is a potential conflict of interest, a planned business activities or an actual or potential competitive risk. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Timeframes for data access may vary and can take up to 6 months or more. Requests for access to data can be submitted via the website www.vivli.org. Questions can also be directed to datasharing@alnylam.com.