HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy

NCT ID: NCT04153149

Last Updated: 2026-01-12

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

655 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-26

Study Completion Date

2026-12-02

Brief Summary

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This study will evaluate the efficacy and safety of vutrisiran 25 mg administered subcutaneously (SC) once every 3 months (q3M) compared to placebo in participants with ATTR amyloidosis with cardiomyopathy.

Detailed Description

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Conditions

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Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Vutrisiran 25 mg

Participants received vutrisiran 25 milligrams (mg) administered subcutaneously (SC) once every 3 months (q3M) during the 36-month double-blind (DB) period. After the DB period, participants continue receiving vutrisiran, 25 mg, SC injection, q3M for up to 24 months in the open-label treatment extension (OLE) period.

Group Type EXPERIMENTAL

Vutrisiran

Intervention Type DRUG

Vutrisiran will be administered by SC injection.

Placebo

Participants received vutrisiran matching placebo administered SC q3M during the 36-month DB period. After the DB period, participants receive vutrisiran, 25 mg, SC injection, q3M for up to 24 months in the OLE period.

Group Type PLACEBO_COMPARATOR

Vutrisiran

Intervention Type DRUG

Vutrisiran will be administered by SC injection.

Sterile Normal Saline (0.9% NaCl)

Intervention Type DRUG

Sterile normal saline (0.9% NaCl) will be administered by SC injection.

Interventions

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Vutrisiran

Vutrisiran will be administered by SC injection.

Intervention Type DRUG

Sterile Normal Saline (0.9% NaCl)

Sterile normal saline (0.9% NaCl) will be administered by SC injection.

Intervention Type DRUG

Other Intervention Names

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ALN-TTRSC02

Eligibility Criteria

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Inclusion Criteria

* Has a documented diagnosis of transthyretin (ATTR) amyloidosis with cardiomyopathy, classified as either hereditary ATTR (hATTR) amyloidosis with cardiomyopathy or wild-type ATTR (wtATTR) amyloidosis with cardiomyopathy meeting pre-specified diagnostic criteria
* Has medical history of heart failure (HF) with at least 1 prior hospitalization for HF OR clinical evidence of HF

Exclusion Criteria

* Has known primary amyloidosis or leptomeningeal amyloidosis
* Has New York Heart Association (NYHA) Class IV heart failure
* Has NYHA Class III heart failure AND is at high risk based on pre-specified criteria
* Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV at the Screening visit
* Has estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m\^2
* Has received prior TTR-lowering treatment
* Has other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathy due to valvular heart disease, or cardiomyopathy due to ischemic heart disease
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alnylam Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Alnylam Pharmaceuticals

Locations

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Clinical Trial Site

La Mesa, California, United States

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Los Angeles, California, United States

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Stanford, California, United States

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Washington D.C., District of Columbia, United States

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Gainesville, Georgia, United States

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Chicago, Illinois, United States

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Evanston, Illinois, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Rochester, Minnesota, United States

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Manhasset, New York, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Cleveland, Ohio, United States

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Allentown, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Houston, Texas, United States

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Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina

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Buenos Aires, Pilar, Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Darlinghurst, New South Wales, Australia

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Northmead, New South Wales, Australia

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Woolloongabba, Queensland, Australia

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Adelaide, South Australia, Australia

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Melbourne, Victoria, Australia

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Graz, , Austria

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Vienna, , Austria

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Vienna, , Austria

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Dendermonde, Oost-Vlaanderen, Belgium

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Ghent, Oost-Vlaanderen, Belgium

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Brussels, , Belgium

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Leuven, , Belgium

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Toronto, Ontario, Canada

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Québec, Quebec, Canada

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Zagreb, , Croatia

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Olomouc, Olomoucký kraj, Czechia

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Prague, Praha, Hlavní Mesto, Czechia

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Odense, Region Syddanmark, Denmark

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Aarhus N, , Denmark

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Créteil, , France

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Marseille, , France

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Paris, , France

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Toulouse, , France

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Frankfurt am Main, Hesse, Germany

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Leipzig, Saxony, Germany

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Essen, , Germany

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Göttingen, , Germany

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Heidelberg, , Germany

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Münster, , Germany

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Würzburg, , Germany

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Budapest, , Hungary

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Budapest, , Hungary

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Szeged, , Hungary

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Dublin, , Ireland

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Dublin, , Ireland

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Haifa, , Israel

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Jerusalem, , Israel

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Ramat Gan, , Israel

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Tsurumai-cho, Aichi-ken, Japan

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Fukuoka, Fukuoka, Japan

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Kurume, Fukuoka, Japan

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Kita-gun, Kagawa-ken, Japan

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Nankoku, Kochi, Japan

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Matsumoto, Nagano, Japan

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Kashihara, Nara, Japan

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Suita, Osaka, Japan

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Suita, Osaka, Japan

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Bunkyo-ku, Tokyo, Japan

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Bunkyo-ku, Tokyo, Japan

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Shinjuku-Ku, Tokyo, Japan

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Fukuoka, , Japan

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Kumamoto, , Japan

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Riga, , Latvia

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Hamra, Beyrouth, Lebanon

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Kaunas, , Lithuania

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Kuantan, Pahang, Malaysia

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Sungai Buloh, Selangor, Malaysia

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Chisinau, , Moldova

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Eindhoven, , Netherlands

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Groningen, , Netherlands

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Utrecht, , Netherlands

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Oslo, , Norway

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San Isidro, Lima region, Peru

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Lima, , Peru

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Wroclaw, Lower Silesian Voivodeship, Poland

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Lodz, Lódzkie, Poland

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Warsaw, Masovian Voivodeship, Poland

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Gdansk, Pomeranian Voivodeship, Poland

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Katowice, , Poland

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Lisbon, Lisbon District, Portugal

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Coimbra, , Portugal

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Faro, , Portugal

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Guimarães, , Portugal

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Porto, , Portugal

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Mecca, Mecca Region, Saudi Arabia

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Riyadh, , Saudi Arabia

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Ljubljana, , Slovenia

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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L'Hospitalet de Llobregat, Barcelona, Spain

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Majadahonda, Madrid, Spain

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Barcelona, , Spain

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Bilbao, , Spain

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Huelva, , Spain

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Málaga, , Spain

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Göteborg, Västerbotten County, Sweden

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Gothenburg, , Sweden

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Chiang Mai, , Thailand

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Bellshill, Lanarkshire, United Kingdom

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London, London, City of, United Kingdom

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Londonderry, Londonderry, United Kingdom

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Hexham, Northumberland, United Kingdom

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Birmingham, , United Kingdom

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Cardiff, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Countries

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United States Argentina Australia Austria Belgium Canada Croatia Czechia Denmark France Germany Hungary Ireland Israel Japan Latvia Lebanon Lithuania Malaysia Moldova Netherlands Norway Peru Poland Portugal Saudi Arabia Slovenia South Korea Spain Sweden Thailand United Kingdom

References

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Jering KS, Fontana M, Lairez O, Longhi S, Azevedo O, Morbach C, Bender S, Jay PY, Vest J, Bulwer BE, Prasad N, Solomon SD, Skali H. Effects of vutrisiran on cardiac structure and function in patients with transthyretin amyloidosis with cardiomyopathy: secondary outcomes of the HELIOS-B trial. Nat Med. 2025 Oct;31(10):3560-3568. doi: 10.1038/s41591-025-03851-z. Epub 2025 Aug 6.

Reference Type DERIVED
PMID: 40770082 (View on PubMed)

Maurer MS, Berk JL, Damy T, Sheikh FH, Gonzalez-Costello J, Morbach C, Delgado D, Bondue A, Azevedo O, Poulsen SH, Jankowska EA, Yang L, Bender S, Eraly SA, Jay PY, Vest J, Fontana M. Impact of Vutrisiran on Cardiac Biomarkers in Patients With Transthyretin Amyloidosis With Cardiomyopathy From HELIOS-B. J Am Coll Cardiol. 2025 Aug 12;86(6):459-475. doi: 10.1016/j.jacc.2025.04.055.

Reference Type DERIVED
PMID: 40769675 (View on PubMed)

Witteles RM, Garcia-Pavia P, Damy T, Grogan M, Sheikh FH, Morbach C, Bender S, Exter J, Eraly SA, Fontana M. Vutrisiran Improves Survival and Reduces Cardiovascular Events in ATTR Amyloid Cardiomyopathy: HELIOS-B. J Am Coll Cardiol. 2025 Apr 30:S0735-1097(25)06170-4. doi: 10.1016/j.jacc.2025.04.008. Online ahead of print.

Reference Type DERIVED
PMID: 40380962 (View on PubMed)

Maurer MS, Witteles RM, Garcia-Pavia P, Sheikh FH, Morbach C, Rodriguez Duque D, Aldinc E, Eraly SA, Gillmore JD. Impact of Heart Failure Severity on Vutrisiran Efficacy in Transthyretin Amyloidosis With Cardiomyopathy. J Am Coll Cardiol. 2025 May 27;85(20):1927-1939. doi: 10.1016/j.jacc.2025.03.477. Epub 2025 Mar 17.

Reference Type DERIVED
PMID: 40099776 (View on PubMed)

Fontana M, Maurer MS, Gillmore JD, Bender S, Aldinc E, Eraly SA, Jay PY, Solomon SD. Outpatient Worsening Heart Failure in Patients With Transthyretin Amyloidosis With Cardiomyopathy in the HELIOS-B Trial. J Am Coll Cardiol. 2025 Feb 25;85(7):753-761. doi: 10.1016/j.jacc.2024.11.015. Epub 2024 Nov 18.

Reference Type DERIVED
PMID: 39566871 (View on PubMed)

Fontana M, Berk JL, Gillmore JD, Witteles RM, Grogan M, Drachman B, Damy T, Garcia-Pavia P, Taubel J, Solomon SD, Sheikh FH, Tahara N, Gonzalez-Costello J, Tsujita K, Morbach C, Pozsonyi Z, Petrie MC, Delgado D, Van der Meer P, Jabbour A, Bondue A, Kim D, Azevedo O, Hvitfeldt Poulsen S, Yilmaz A, Jankowska EA, Algalarrondo V, Slugg A, Garg PP, Boyle KL, Yureneva E, Silliman N, Yang L, Chen J, Eraly SA, Vest J, Maurer MS; HELIOS-B Trial Investigators. Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. N Engl J Med. 2025 Jan 2;392(1):33-44. doi: 10.1056/NEJMoa2409134. Epub 2024 Aug 30.

Reference Type DERIVED
PMID: 39213194 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2023-508366-15-00

Identifier Type: CTIS

Identifier Source: secondary_id

ALN-TTRSC02-003

Identifier Type: -

Identifier Source: org_study_id

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