TRITON-CM: A Study to Evaluate Nucresiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
TRITON-CM: A Phase 3 Global, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Transthyretin-Mediated Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
2 other identifiers
interventional
1,250
31 countries
201
Brief Summary
The purpose of this study is to:
- Evaluate the efficacy of nucresiran compared to placebo on reducing all-cause mortality and cardiovascular (CV) events
- Evaluate the efficacy of nucresiran compared to placebo on additional assessments of CV events and/or death
- Evaluate the efficacy of nucresiran compared to placebo on patient-reported health status and health-related quality of life
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2025
Longer than P75 for phase_3
201 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
June 30, 2025
CompletedStudy Start
First participant enrolled
July 2, 2025
CompletedFirst Posted
Study publicly available on registry
July 8, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 28, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 30, 2032
April 17, 2026
April 1, 2026
4.9 years
June 30, 2025
April 16, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Composite outcome of all-cause mortality and recurrent cardiovascular [CV] events (CV hospitalizations and urgent heart failure [HF] visits)
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) will be compared between treatment groups using an Andersen-Gill model.
Baseline to end of double-blind period (estimated 32 months, maximum 5 years)
Secondary Outcomes (4)
Time to first CV event (CV hospitalizations and urgent HF visits) or all-cause mortality
Baseline to end of double-blind period (estimated 32 months, maximum 5 years)
All-cause mortality
Baseline to end of double-blind period (estimated 32 months, maximum 5 years)
Recurrent CV events (CV hospitalizations and urgent HF visits)
Baseline to end of double-blind period (estimated 32 months, maximum 5 years)
Change from baseline in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS)
Baseline to Month 30
Study Arms (2)
Placebo
PLACEBO COMPARATORParticipants will receive placebo administered subcutaneously (SC) once every 6 months (q6M) during the double-blind (DB) period, followed by nucresiran 300 mg administered SC q6M during the open-label extension (OLE) period.
Nucresiran 300 mg
EXPERIMENTALParticipants will receive nucresiran 300 mg administered SC Q6M during the DB period, followed by nucresiran 300 mg administered SC q6M during the OLE period.
Interventions
Sterile Normal Saline (0.9% NaCl) administered SC once q6M
Nucresiran 300 mg administered SC q6M
Eligibility Criteria
You may qualify if:
- Has documented diagnosis of ATTR amyloidosis with cardiomyopathy including those with hereditary ATTR (hATTR) or wild-type ATTR (wATTR) amyloidosis.
- Has medical history of heart failure (HF) with at least 1 prior hospitalization for HF or signs and symptoms that require treatment with a diuretic.
- Has screening N-terminal prohormone B-type natriuretic peptide (NT-proBNP) \>300 ng/L and \<8500 ng/L; In patients with permanent or persistent atrial fibrillation, screening NT-proBNP \>600 ng/L and \<8500 ng/L.
- Patients may be receiving approved TTR stabilizers for ATTR amyloidosis (eg, tafamidis, acoramidis) and may be receiving background therapy for HF at the discretion of the Investigator.
You may not qualify if:
- Has New York Heart Association (NYHA) Class IV HF; or NYHA Class III heart failure AND ATTR Amyloidosis Disease Stage 3.
- Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV.
- Has an estimated glomerular filtration rate eGFR of \<30 mL/min/1.73m\^2 at screening.
- Has received prior or currently receiving TTR-lowering therapy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (207)
Clinical Trial Site
La Jolla, California, 92037, United States
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Stanford, California, 94305, United States
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Norwich, Connecticut, 06360, United States
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Washington D.C., District of Columbia, 20010, United States
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Brandon, Florida, 33511, United States
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Miami, Florida, 33125, United States
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Atlanta, Georgia, 30309, United States
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Gainesville, Georgia, 30501, United States
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Tucker, Georgia, 30084, United States
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Indianapolis, Indiana, 46202, United States
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Indianapolis, Indiana, 46260, United States
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Kansas City, Kansas, 66160, United States
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Baltimore, Maryland, 21287, United States
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Boston, Massachusetts, 02115, United States
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Boston, Massachusetts, 02118, United States
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Detroit, Michigan, 48202, United States
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Rochester, Minnesota, 55905, United States
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St Louis, Missouri, 63110, United States
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Manhasset, New York, 11030, United States
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New York, New York, 10029, United States
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New York, New York, 10032, United States
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New York, New York, 10065, United States
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The Bronx, New York, 10467, United States
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Charlotte, North Carolina, 28204, United States
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Cleveland, Ohio, 44195, United States
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Lancaster, Pennsylvania, 17602, United States
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Philadelphia, Pennsylvania, 19104, United States
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Dallas, Texas, 75246, United States
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Houston, Texas, 77030, United States
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Plano, Texas, 75024, United States
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Salt Lake City, Utah, 84132, United States
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Charlottesville, Virginia, 22903, United States
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Norfolk, Virginia, 23507, United States
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Spokane, Washington, 99204, United States
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Buenos Aires, C1025ABI, Argentina
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Buenos Aires, C1093AAS, Argentina
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Buenos Aires, C1199ABB, Argentina
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Buenos Aires, C1428, Argentina
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Rosario, S2000DEJ, Argentina
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Rosario, S2000DSR, Argentina
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Rosario, S2000GAP, Argentina
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Adelaide, 5000, Australia
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Bedford Park, 5042, Australia
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Box Hill, 3128, Australia
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Chermside, 4032, Australia
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Darlinghurst, 2010, Australia
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Joondalup, 6027, Australia
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Westmead, 2145, Australia
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Braunau am Inn, 5280, Austria
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Graz, 8036, Austria
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Vienna, 1090, Austria
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Vienna, 1160, Austria
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Vienna, 1210, Austria
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Wels, 4600, Austria
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Aalst, 9300, Belgium
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Bruges, 8000, Belgium
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Brussels, 1200, Belgium
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Dendermonde, 9200, Belgium
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Genk, 3600, Belgium
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Ghent, 9000, Belgium
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Hasselt, 3500, Belgium
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Leuven, 3000, Belgium
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Liège, 4000, Belgium
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Roeselare, 8800, Belgium
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Belo Horizonte, 30220-140, Brazil
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Porto Alegre, 90035-903, Brazil
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Porto Alegre, 90560-032, Brazil
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Ribeirão Preto, 14026-900, Brazil
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Ribeirão Preto, 14051-140, Brazil
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Salvador, 40170-130, Brazil
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São Paulo, 04038-002, Brazil
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São Paulo, 05403-000, Brazil
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London, N6A 5A5, Canada
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Santiago, 7500588, Chile
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Santiago, 8320000, Chile
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Dongcheng, 100006, China
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Brno, 602 00, Czechia
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Ostrava, 708-52, Czechia
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Prague, 128 21, Czechia
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Aarhus N, 8200, Denmark
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København Ø, 2100, Denmark
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Odense C, 5000, Denmark
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Chambray-lès-Tours, 37170, France
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Dijon, 21000, France
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La Tronche, 38700, France
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Marseille, 13005, France
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Martinique, 97261, France
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Montpellier, 34295, France
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Paris, 75015, France
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Paris, 75018, France
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Pessac, 33600, France
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Reims, 51100, France
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Rennes, 35000, France
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Rouen, 76031, France
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Saint-Herblain, 44093, France
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Strasbourg, 67091, France
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Toulouse, 31059, France
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Berlin, 13353, Germany
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Cologne, 50937, Germany
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Göttingen, 37075, Germany
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Hanover, 30625, Germany
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Leipzig, 04103, Germany
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Munich, 81377, Germany
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Münster, 48149, Germany
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Würzburg, 97080, Germany
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Athens, 115 27, Greece
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Athens, 115 28, Greece
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Heraklion, 714 09, Greece
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Thessaloniki, 546 36, Greece
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Hong Kong, 999077, Hong Kong
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Budapest, 1085, Hungary
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Be’er Ya‘aqov, 70300, Israel
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Haifa, 3109601, Israel
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Jerusalem, 91120, Israel
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Petah Tikva, 4941492, Israel
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Ancona, 60126, Italy
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Bologna, 40138, Italy
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Brescia, 25123, Italy
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Florence, 50134, Italy
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Forlì, 47121, Italy
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Milan, 20122, Italy
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Naples, 80131, Italy
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Padova, 35128, Italy
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Pavia, 27100, Italy
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Pisa, 56124, Italy
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Rimini, 47923, Italy
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Roma, 00168, Italy
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Rome, 00161, Italy
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Torino, 10126, Italy
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Bunkyō City, 113-8655, Japan
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Fukuoka, 810-0001, Japan
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Fukuoka, 812-8582, Japan
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Kagawa, 761-0793, Japan
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Kashihara, 634-8522, Japan
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Kobe, 650-0017, Japan
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Kumamoto, 860-8556, Japan
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Kurume, 830-0011, Japan
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Matsumoto-shi, 390-8621, Japan
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Nagoya, 466-8560, Japan
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Nankoku, 783-0043, Japan
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Niigata, 951-8520, Japan
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Okayama, 700-8558, Japan
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Sapporo, 060-8543, Japan
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Sapporo, 060-8648, Japan
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Sendai, 980-8574, Japan
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Suita, 564-8565, Japan
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Tokyo, 160-8582, Japan
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Kajang, 43000, Malaysia
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Kuala Lumpur, 59100, Malaysia
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Eindhoven, 5623 EJ, Netherlands
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Groningen, 9713 GZ, Netherlands
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Maastricht, 6229 HX, Netherlands
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Rotterdam, 3015 GD, Netherlands
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Utrecht, 3584 CX, Netherlands
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Christchurch, 8011, New Zealand
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Hamilton, 3204, New Zealand
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Ålesund, 6017, Norway
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Lørenskog, 1478, Norway
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Carnaxide, 2790-134, Portugal
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Creixomil, 4835-044, Portugal
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Leiria, 2410-197, Portugal
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Lisbon, 1169-024, Portugal
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Lisbon, 1649-035, Portugal
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Vila Real, 5000-508, Portugal
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Viseu, 3504-509, Portugal
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Bucharest, 022328, Romania
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Cluj-Napoca, 400001, Romania
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Košice, 040 11, Slovakia
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Incheon, 22332, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 06351, South Korea
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Seoul, 06591, South Korea
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A Coruña, 15006, Spain
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Barcelona, 08035, Spain
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Barcelona, 08036, Spain
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Bilbao, 48013, Spain
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El Palmar, 30120, Spain
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Huelva, 21005, Spain
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Jaén, 23007, Spain
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L'Hospitalet de Llobregat, 8907, Spain
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Lleida, 25198, Spain
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Madrid, 28046, Spain
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Madrid, 28222, Spain
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Palma de Mallorca, 07198, Spain
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Pamplona, 31008, Spain
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Salamanca, 37007, Spain
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Santiago de Compostela, 15706, Spain
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Valencia, 46010, Spain
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Valencia, 46026, Spain
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Vigo, 36213, Spain
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Gothenburg, 413 45, Sweden
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Lund, 222 42, Sweden
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Solna, 171 76, Sweden
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Basel, 4051, Switzerland
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Geneva, 1205, Switzerland
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Lucerne, 6000, Switzerland
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Sankt Gallen, 9007, Switzerland
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New Taipei City, 220, Taiwan
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Taipei, 10002, Taiwan
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Taipei, 112, Taiwan
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Bellshill, ML4 3NJ, United Kingdom
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Birmingham, B15 2SQ, United Kingdom
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Cardiff, CF15 9SS, United Kingdom
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London, NW10 2PB, United Kingdom
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London, NW3 2QG, United Kingdom
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Manchester, M15 6SE, United Kingdom
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
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 30, 2025
First Posted
July 8, 2025
Study Start
July 2, 2025
Primary Completion (Estimated)
May 28, 2030
Study Completion (Estimated)
November 30, 2032
Last Updated
April 17, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
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.