Hereditary Transthyretin-Mediated Amyloidosis With PolyneuropathyPhase 3TRITON-PNNCT07223203
TRITON-PN: A Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy
A Phase 3 study testing Nucresiran and Vutrisiran in people with Hereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy and hATTR-PN, run by Alnylam Pharmaceuticals at 61 sites in 22 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Hereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy, hATTR-PN
- What is being tested?
- Nucresiran and Vutrisiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- 61 sitesin 22 countries
- Study dates
- 3 Feb 2026to 12 Jun 2031
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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 locations and contacts
61 sites in 22 countries. Contact the study team or a site near you to ask about taking part.
61 sites in 22 countries
United States11 sites, 11 recruiting
- Recruiting
Clinical Trial Site
Aurora, Colorado, 80045
- Recruiting
Clinical Trial Site
Baltimore, Maryland, 21287
- Recruiting
Clinical Trial Site
Boston, Massachusetts, 02118
- Recruiting
Clinical Trial Site
Chapel Hill, North Carolina, 27514
- Recruiting
Clinical Trial Site
Chicago, Illinois, 60611
- Recruiting
Clinical Trial Site
Dallas, Texas, 75246
- Recruiting
Clinical Trial Site
Houston, Texas, 77030
- Recruiting
Clinical Trial Site
Nashville, Tennessee, 37232
- Recruiting
Clinical Trial Site
New York, New York, 10016
- Recruiting
Clinical Trial Site
New York, New York, 10032
- Recruiting
Clinical Trial Site
Rochester, Minnesota, 55905
Brazil5 sites, 5 recruiting
- Recruiting
Clinical Trial Site
Ribeirão Preto, 14051-140
- Recruiting
Clinical Trial Site
Rio de Janeiro, 22640-100
- Recruiting
Clinical Trial Site
Rio de Janeiro, 22775-001
- Recruiting
Clinical Trial Site
Salvador, 40290-000
- Recruiting
Clinical Trial Site
São Paulo, 04038-002
Italy5 sites, 5 recruiting
- Recruiting
Clinical Trial Site
Florence, 50134
- Recruiting
Clinical Trial Site
Milan, 20133
- Recruiting
Clinical Trial Site
Padova, 35128
- Recruiting
Clinical Trial Site
Pavia, 27100
- Recruiting
Clinical Trial Site
Roma, 00168
Spain5 sites, 5 recruiting
- Recruiting
Clinical Trial Site
Barcelona, 08035
- Recruiting
Clinical Trial Site
Huelva, 21005
- Recruiting
Clinical Trial Site
L'Hospitalet de Llobregat, 8907
- Recruiting
Clinical Trial Site
Madrid, 28040
- Recruiting
Clinical Trial Site
Palma de Mallorca, 07198
Japan4 sites, 4 recruiting
- Recruiting
Clinical Trial Site
Bunkyo C, 113-8519
- Recruiting
Clinical Trial Site
Kumamoto, 860-8556
- Recruiting
Clinical Trial Site
Matsumoto-shi, 390-8621
- Recruiting
Clinical Trial Site
Suita, 565-0871
France3 sites, 3 recruiting
- Recruiting
Clinical Trial Site
Créteil, 94000
- Recruiting
Clinical Trial Site
Le Kremlin-Bicêtre, 94270
- Recruiting
Clinical Trial Site
Marseille, 13005
Germany3 sites, 3 recruiting
- Recruiting
Clinical Trial Site
Berlin, 10117
- Recruiting
Clinical Trial Site
Heidelberg, 69120
- Recruiting
Clinical Trial Site
Münster, 48149
Taiwan3 sites, 3 recruiting
- Recruiting
Clinical Trial Site
Taipei, 10002
- Recruiting
Clinical Trial Site
Taipei, 112
- Recruiting
Clinical Trial Site
Taoyuan City, 33305
Argentina2 sites, 2 recruiting
- Recruiting
Clinical Trial Site
Belgrano, C1428AQK
- Recruiting
Clinical Trial Site
Rosario, CP2000
Australia2 sites, 2 recruiting
- Recruiting
Clinical Trial Site
Darlinghurst, 2010
- Recruiting
Clinical Trial Site
Woolloongabba, 4102
Greece2 sites, 2 recruiting
- Recruiting
Clinical Trial Site
Athens, 115 28
- Recruiting
Clinical Trial Site
Heraklion, 715 00
Mexico2 sites, 2 recruiting
- Recruiting
Clinical Trial Site
Guadalajara, 44670
- Recruiting
Clinical Trial Site
Tlalpan, 14080
Portugal2 sites, 2 recruiting
- Recruiting
Clinical Trial Site
Lisbon, 1649-035
- Recruiting
Clinical Trial Site
Porto, 4099-001
South Korea2 sites, 2 recruiting
- Recruiting
Clinical Trial Site
Seoul, 05030
- Recruiting
Clinical Trial Site
Seoul, 06351
Sweden2 sites, 2 recruiting
- Recruiting
Clinical Trial Site
Stockholm, 113 61
- Recruiting
Clinical Trial Site
Umeå, 907 37
Turkey (Türkiye)2 sites, 2 recruiting
- Recruiting
Clinical Trial Site
Istanbul, 34093
- Recruiting
Clinical Trial Site
Izmir, 35330
Malaysia1 site, 1 recruiting
- Recruiting
Clinical Trial Site
Kuala Lumpur, 59100
United Kingdom1 site, 1 recruiting
- Recruiting
Clinical Trial Site
London, NW3 2QG
About this study
Official title: 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)
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
- Being tested
- Nucresiran, Vutrisiran
- Keywords
- Polyneuropathy, Amyloidosis, Transthyretin, TTR, RNAi therapeutic
- Medical subject headings
- Polyneuropathies, Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NucresiranDrug
Also called ALN-TTRSC04
Nucresiran 300 mg administered SC q6M
VutrisiranDrug
Also called AMVUTTRA, ALN-TTRSC02
Vutrisiran 25 mg administered SC q3M
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Nucresiran; Drug: Vutrisiran |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: Baseline and Month 9
Percent Reduction in Serum TTR Levels in the Nucresiran Group Compared to the In-study Vutrisiran Group through Month 9
Measured: 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.
Measured: 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
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.
Measured: 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
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.
Measured: Baseline and Month 18
Change from Baseline in mBMI Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18
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.
Measured: Baseline and Month 18
Change from Baseline in Rasch-built Overall Disability Scale (R-ODS) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18
The R-ODS is a patient-reported measure of level of disability on a scale of 0-48, with 0 being the worst and 48 the best (no limitations); scores are based on activities of daily living and social participation. An increase in R-ODS from baseline suggests improvement in disability, and a decrease from baseline suggests worsening of disability.
Measured: Baseline and Month 18
Change from Baseline in Timed 10-meter Walk Test (10-MWT) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 18
The timed 10-MWT is a measure of ambulatory ability and measures the time (in seconds) that it takes a participant to walk 10 meters (gait speed). An increase in gait speed from baseline represents improvement, and a decrease from baseline represents worsening.
Measured: Baseline and Month 18
Percent Reduction in Serum TTR Levels in the Nucresiran Group Compared to the In-study Vutrisiran Group through Month 18
Measured: Up to Month 18
Percent Reduction in Serum TTR Levels in the Nucresiran Group Compared to the In-study Vutrisiran Group at Week 6
Measured: Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2025
- Study start3 Feb 2026
- Primary completion27 Dec 2027 (estimated)
- Study completion12 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Transthyretin-Mediated Amyloidosis With PolyneuropathyStudies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 125 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07223203
- Sponsor's protocol ID
- ALN-TTRSC04-004
- Other IDs
- 2025-522544-40-00, 2025
- Acronym
- TRITON-PN
- Status last verified
- Oct 2026
- First submitted
- 29 Oct 2025
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.