Transthyretin Amyloidosis (ATTR) With CardiomyopathyPhase 3NCT04153149
HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
A Phase 3 study testing Vutrisiran and Sterile Normal Saline (0.9% NaCl) in people with Transthyretin Amyloidosis (ATTR) With Cardiomyopathy, run by Alnylam Pharmaceuticals at 121 sites in 33 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
- What is being tested?
- Vutrisiran and Sterile Normal Saline (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 655 participants
- Where
- 121 sitesin 33 countries
- Study dates
- 26 Nov 2019to 13 Jan 2027
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 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
Who cannot join
- 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
Trial locations and contacts
121 sites in 33 countries.
121 sites in 33 countries
United States17 sites
Clinical Trial Site
Allentown, Pennsylvania, 18103
Clinical Trial Site
Boston, Massachusetts, 02115
Clinical Trial Site
Boston, Massachusetts, 02118
Clinical Trial Site
Chicago, Illinois, 60637
Clinical Trial Site
Cleveland, Ohio, 44195
Clinical Trial Site
Durham, North Carolina, 27710
Clinical Trial Site
Evanston, Illinois, 60201
Clinical Trial Site
Gainesville, Georgia, 30501
Clinical Trial Site
Houston, Texas, 77030
Clinical Trial Site
La Mesa, California, 91942
Clinical Trial Site
Los Angeles, California, 90033
Clinical Trial Site
Manhasset, New York, 11030
Clinical Trial Site
New York, New York, 10032
Clinical Trial Site
Philadelphia, Pennsylvania, 19104
Clinical Trial Site
Rochester, Minnesota, 55902
Clinical Trial Site
Stanford, California, 94305
Clinical Trial Site
Washington D.C., District of Columbia, 20010
Japan14 sites
Clinical Trial Site
Bunkyō City, 113-8431
Clinical Trial Site
Bunkyō City, 113-8655
Clinical Trial Site
Fukuoka, 810-0001
Clinical Trial Site
Fukuoka, 812-8582
Clinical Trial Site
Kashihara, 634-8522
Clinical Trial Site
Kita-gun, 761-0793
Clinical Trial Site
Kumamoto, 860-8556
Clinical Trial Site
Kurume, 830-0011
Clinical Trial Site
Matsumoto, 390-8621
Clinical Trial Site
Nankoku, 783-8505
Clinical Trial Site
Shinjuku-Ku, 160-8582
Clinical Trial Site
Suita, 564-8565
Clinical Trial Site
Suita, 565-0871
Clinical Trial Site
Tsurumai-cho, 466-8560
United Kingdom8 sites
Clinical Trial Site
Bellshill, ML4 3NJ
Clinical Trial Site
Birmingham, B15 2SQ
Clinical Trial Site
Cardiff, CF15 9SS
Clinical Trial Site
Hexham, NE46 1QJ
Clinical Trial Site
London, NW3 2QG
Clinical Trial Site
London, SE1 1YR
Clinical Trial Site
Londonderry, BT47 6SB
Clinical Trial Site
Manchester, M15 6SE
Germany7 sites
Clinical Trial Site
Essen, 45122
Clinical Trial Site
Frankfurt am Main, 60313
Clinical Trial Site
Göttingen, 37075
Clinical Trial Site
Heidelberg, 69120
Clinical Trial Site
Leipzig, 04103
Clinical Trial Site
Münster, 48149
Clinical Trial Site
Würzburg, 97078
Poland6 sites
Clinical Trial Site
Cracow, 31-202
Clinical Trial Site
Gdansk, 80-382
Clinical Trial Site
Katowice, 40-555
Clinical Trial Site
Lodz, 90-127
Clinical Trial Site
Warsaw, 01-192
Clinical Trial Site
Wroclaw, 50-556
Spain6 sites
Clinical Trial Site
Barcelona, 08035
Clinical Trial Site
Bilbao, 48013
Clinical Trial Site
Huelva, 21005
Clinical Trial Site
L'Hospitalet de Llobregat, 08907
Clinical Trial Site
Majadahonda, 28222
Clinical Trial Site
Málaga, 29010
Australia5 sites
Clinical Trial Site
Adelaide, 5000
Clinical Trial Site
Darlinghurst, 2010
Clinical Trial Site
Melbourne, 3004
Clinical Trial Site
Northmead, 2152
Clinical Trial Site
Woolloongabba, 4102
Portugal5 sites
Clinical Trial Site
Coimbra, 3000-075
Clinical Trial Site
Faro, 8000-386
Clinical Trial Site
Guimarães, 4835-044
Clinical Trial Site
Lisbon, 1649-035
Clinical Trial Site
Porto, 4099-001
Argentina4 sites
Clinical Trial Site
Buenos Aires, B1629ODT
Clinical Trial Site
Buenos Aires, C1093AAS
Clinical Trial Site
Buenos Aires, C1199ABB
Clinical Trial Site
Buenos Aires, C1428ART
Belgium4 sites
Clinical Trial Site
Brussels, 1070
Clinical Trial Site
Dendermonde, 9200
Clinical Trial Site
Ghent, 9000
Clinical Trial Site
Leuven, 3000
France4 sites
Clinical Trial Site
Créteil, 94000
Clinical Trial Site
Marseille, 13385
Clinical Trial Site
Paris, 75877
Clinical Trial Site
Toulouse, 31059
South Korea4 sites
Clinical Trial Site
Seoul, 03080
Clinical Trial Site
Seoul, 03722
Clinical Trial Site
Seoul, 06351
Clinical Trial Site
Seoul, 06591
Austria3 sites
Clinical Trial Site
Graz, 8036
Clinical Trial Site
Vienna, 1090
Clinical Trial Site
Vienna, 1210
Hungary3 sites
Clinical Trial Site
Budapest, 1088
Clinical Trial Site
Budapest, 1134
Clinical Trial Site
Szeged, 6725
Israel3 sites
Clinical Trial Site
Haifa, 3339419
Clinical Trial Site
Jerusalem, 9112000
Clinical Trial Site
Ramat Gan, 5262000
Netherlands3 sites
Clinical Trial Site
Eindhoven, 5623 EJ
Clinical Trial Site
Groningen, 9713 GZ
Clinical Trial Site
Utrecht, 3584 CW
Peru3 sites
Clinical Trial Site
Callao - Vellavista, 7016
Clinical Trial Site
Lima - San Miguel, 15088
Clinical Trial Site
San Isidro, 15076
Canada2 sites
Clinical Trial Site
Québec, G1V4G5
Clinical Trial Site
Toronto, M5G 2C4
Czechia2 sites
Clinical Trial Site
Olomouc, 779 00
Clinical Trial Site
Prague, 12000
Denmark2 sites
Clinical Trial Site
Aarhus N, 8200
Clinical Trial Site
Odense, 5000
Ireland2 sites
Clinical Trial Site
Dublin, D07 A8NN
Clinical Trial Site
Dublin, Dublin 8
Malaysia2 sites
Clinical Trial Site
Kuantan, 25100
Clinical Trial Site
Sungai Buloh, 47000
Saudi Arabia2 sites
Clinical Trial Site
Mecca, 21955
Clinical Trial Site
Riyadh, 12372
About this study
Official title: HELIOS-B: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
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.
- Being tested
- Vutrisiran, Sterile Normal Saline (0.9% NaCl)
- Keywords
- ATTR, Cardiomyopathy, Amyloidosis, TTR, Transthyretin, TTR-mediated amyloidosis, Amyloidosis, Hereditary, Amyloidosis, Hereditary, Transthyretin-Related, Familial Amyloidosis, RNAi therapeutic, Transthyretin amyloid cardiomyopathy, TTR cardiomyopathy, ATTR-CM, Wild-type TTR, V122I, TTR amyloidosis, Amyloidosis, Wild Type
- Medical subject headings
- Amyloidosis, Hereditary, Transthyretin-Related, Cardiomyopathies, Amyloidosis, Amyloidosis, Familial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VutrisiranDrug
Also called ALN-TTRSC02
Vutrisiran will be administered by SC injection.
Sterile Normal Saline (0.9% NaCl)Drug
Sterile normal saline (0.9% NaCl) will be administered by SC injection.
| Study group | Role | What they receive |
|---|---|---|
| Vutrisiran 25 mg | Experimental | 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. Receives: Drug: Vutrisiran |
| Placebo | Placebo comparator | 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. Receives: Drug: Vutrisiran; Drug: Sterile Normal Saline (0.9% NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) in the Overall Population
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) were compared between treatment groups using a modified Andersen-Gill model with a robust variance. All-cause mortality included heart transplantation and LVAD placement events along with deaths; recurrent CV events included CV hospitalizations and urgent HF visits. The number of participants with at least one CV event or all-cause mortality event have been reported here. No imputation was done for participants who dropped out early for the primary analysis of this composite outcome endpoint.
Measured: Up to Month 36
Composite Endpoint of All-Cause Mortality and Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) in the Vutrisiran Monotherapy Subgroup
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) were compared between treatment groups using a modified Andersen-Gill model with a robust variance. All-cause mortality included heart transplantation and LVAD placement events along with deaths; recurrent CV events included CV hospitalizations and urgent HF visits. The number of participants with at least one CV event or all-cause mortality event have been reported here. No imputation was done for participants who dropped out early for the primary analysis of this composite outcome endpoint.
Measured: Up to Month 36
Secondary outcomes (7)
Change From Baseline in 6-Minute Walk Test (6-MWT) in the Overall Population
The 6-MWT is an assessment of functional exercise capacity. Participants are instructed to walk back and forth along a flat, straight path, typically 30 meters in length, for a duration of 6 minutes. The total distance covered in meters is recorded at the end of 6 minutes. A longer distance reflects a better outcome. Analysis was based on the mixed-effect model of repeated measures (MMRM). Missing change values due to amyloidosis disease progression and death were imputed using sampling with replacement from the worst 10% of observed values, as specified in the statistical analysis plan (SAP).
Measured: Baseline to Month 30
Change From Baseline in 6-MWT in the Vutrisiran Monotherapy Subgroup
The 6-MWT is an assessment of functional exercise capacity. Participants are instructed to walk back and forth along a flat, straight path, typically 30 meters in length, for a duration of 6 minutes. The total distance covered in meters is recorded at the end of 6 minutes. A longer distance reflects a better outcome. Analysis was based on the MMRM. Missing change values due to amyloidosis disease progression and death were imputed using sampling with replacement from the worst 10% of observed values, as specified in the SAP.
Measured: Baseline to Month 30
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score in the Overall Population
The KCCQ is a 23-item self-administered questionnaire quantifying 6 domains (symptoms [frequency and burden], physical function, quality of life (QoL), social limitation, self-efficacy, and symptom stability) and 2 summary scores (clinical and overall summary [OS]). Scores were generated for each domain and transformed to a range of 0-100, in which higher scores reflect better health status. KCCQ- overall summary score was average of domains- physical function, total symptoms (average of symptom frequency and burden), QoL, and social limitation, and transformed to a single score which ranged from 0 (worst) - 100 (the best possible status), where the higher score reflected better health status. Analysis was based on the MMRM.
Measured: Baseline to Month 30
Change From Baseline in the KCCQ-OS Score in the Vutrisiran Monotherapy Subgroup
The KCCQ is a 23-item self-administered questionnaire quantifying 6 domains (symptoms [frequency and burden], physical function, QoL, social limitation, self-efficacy, and symptom stability) and 2 summary scores (clinical and OS). Scores were generated for each domain and transformed to a range of 0-100, in which higher scores reflect better health status. KCCQ- overall summary score was average of domains- physical function, total symptoms (average of symptom frequency and burden), QoL, and social limitation, and transformed to a single score which ranged from 0 (worst) - 100 (the best possible status), where the higher score reflected better health status. Analysis was based on the MMRM.
Measured: Baseline to Month 30
All-cause Mortality in the Overall Population and Vutrisiran Monotherapy Subgroup
All-cause mortality also included heart transplantation and LVAD placement events along with deaths; recurrent CV events included CV hospitalizations and urgent HF visits.
Measured: Up to 42 months
Percentage of Participants With Change in NYHA Class at Month 30 in the Overall Population
NYHA class is a clinical assessment of symptoms resulting from heart failure. In NYHA functional classification system places participants in 1 of 4 categories based on limitations of physical activity. Class I denotes no symptoms and no limitation of physical activity; II, slight limitation, resulting in symptoms with ordinary physical activity; III, marked limitation, resulting in symptoms with less than ordinary physical activity; and IV, symptoms at rest. Here, the participants with a change in NYHA class have been reported in two categories:
- participants who had no change or had improvement in the NYHA class (lower class) from baseline and 2) participants who had a worsened NYHA class from baseline (higher class).
Values have been rounded off to a single decimal.
Measured: Baseline to Month 30
Percentage of Participants With Change in NYHA Class at Month 30 in the Vutrisiran Monotherapy Subgroup
NYHA class is a clinical assessment of symptoms resulting from heart failure. In NYHA functional classification system places participants in 1 of 4 categories based on limitations of physical activity. Class I denotes no symptoms and no limitation of physical activity; II, slight limitation, resulting in symptoms with ordinary physical activity; III, marked limitation, resulting in symptoms with less than ordinary physical activity; and IV, symptoms at rest. Here, the participants with a change in NYHA class have been reported in two categories:
- participants who had no change or had improvement in the NYHA class (lower class) from baseline and 2) participants who had a worsened NYHA class from baseline (higher class).
Values have been rounded off to a single decimal.
Measured: Baseline to Month 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2019
- Study start26 Nov 2019
- Primary completion8 May 2024
- Study completion13 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Transthyretin Amyloidosis (ATTR) With CardiomyopathyStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 655 participants (actual)
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
- NCT04153149
- Sponsor's protocol ID
- ALN-TTRSC02-003
- Other IDs
- 2023-508366-15-00, 2023
- Status last verified
- Oct 2026
- First submitted
- 4 Nov 2019
- Last updated
- 2 Nov 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Hamatani Y, Claggett BL, Cuddy SAM, Sarswat N, Vaishnav J, Grogan M, Maurer MS, Witteles RM, Gonzalez-Lopez E, Garcia-Pavia P, Sheikh FH, Drachman BM, Kosheleff A, Bansilal S, Gillmore JD, Fontana M, Solomon SD. Effect of Vutrisiran According to Baseline Tafamidis Use in Transthyretin Amyloidosis With Cardiomyopathy: Insights From HELIOS-B. J Am Coll Cardiol. 2026 Aug 30:S0735-1097(26)07208-6. doi: 10.1016/j.jacc.2026.07.022. Online ahead of print.
PubMed 42669070Abovich A, Fontana M, Claggett B, Gillmore JD, Cappelli F, Ambardekar AV, Morbach C, Garcia-Pavia P, Witteles RM, Maurer MS, Jay PY, Kosheleff A, Bansilal S, Solomon SD. Influence of Disease-Modifying Therapy on the Efficacy of Vutrisiran in Transthyretin Cardiac Amyloidosis. J Am Coll Cardiol. 2026 Aug 5:S0735-1097(26)07209-8. doi: 10.1016/j.jacc.2026.07.023. Online ahead of print.
PubMed 42669069Gillmore JD, Hamatani Y, Fontana M, Vaduganathan M, Claggett BL, Garcia-Pavia P, Masri A, Cappelli F, Grogan M, Morbach C, Maurer MS, Solomon SD. Gene Silencer Therapy in Transthyretin Amyloid Cardiomyopathy: A Meta-Analysis of Outcomes Trials. JAMA. 2026 Aug 30. doi: 10.1001/jama.2026.17246. Online ahead of print.
PubMed 42669065Jering KS, Manafi A, Claggett BL, Fontana M, Gillmore JD, Bulwer BE, Roshanali F, Prasad N, Jay PY, Solomon SD, Skali H. Right Ventricular Function, Clinical Outcomes, and Effect of Vutrisiran in Transthyretin Amyloidosis With Cardiomyopathy: Secondary Analysis of the HELIOS-B Randomized Clinical Trial. JAMA Cardiol. 2026 Aug 26. doi: 10.1001/jamacardio.2026.3390. Online ahead of print.
PubMed 42646924Jering KS, Manafi A, Claggett BL, Bart NK, Prasad N, Birkhoelzer SM, Hamatani Y, Lairez O, Tsujita K, Gillmore JD, Maurer MS, Jay PY, Skali H, Fontana M, Solomon SD. Left Atrial Structure and Function, Clinical Outcomes, and Efficacy of Vutrisiran in Transthyretin Amyloidosis With Cardiomyopathy: A Secondary Analysis of the HELIOS-B Randomized Clinical Trial. JAMA Cardiol. 2026 Aug 19:e262992. doi: 10.1001/jamacardio.2026.2992. Online ahead of print.
PubMed 42616515Fontana M, Algalarrondo V, Garcia-Pavia P, Maurer MS, Gillmore JD, Cappelli F, Kolachana K, Gao X, Jadhav S, Mehrotra N, Robbie G, Badri P. Vutrisiran-Mediated Knockdown of Transthyretin in Patients with ATTR Amyloidosis. Clin Pharmacokinet. 2026 Jul;65(7):1073-1085. doi: 10.1007/s40262-026-01651-3. Epub 2026 May 27.
PubMed 42201475Endo J, Minamino T, Oh J, Tahara N, Tsujita K, Izumi C, Okumura T, Onoue K, Kitaoka H, Chen C, Chan-Daniels A, Kim D. Vutrisiran in East Asian Patients With Transthyretin Amyloidosis With Cardiomyopathy: Post-Hoc Analysis of HELIOS-B. JACC Asia. 2026 Aug;6(8 Pt 1):1517-1527. doi: 10.1016/j.jacasi.2026.03.031. Epub 2026 May 21.
PubMed 42165759Claggett BL, Fontana M, Vaduganathan M, Hamatani Y, Maurer MS, Gillmore JD, Solomon SD. Timing of Mortality Benefit in Outcomes Trials in Transthyretin Amyloidosis. J Am Coll Cardiol. 2026 Feb 10;87(5):522-529. doi: 10.1016/j.jacc.2025.09.1512. Epub 2025 Sep 25.
PubMed 41225306Jering 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.
PubMed 40770082Maurer 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.
PubMed 40769675Witteles 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.
PubMed 40380962Maurer 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.
PubMed 40099776Fontana 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.
PubMed 39566871Fontana 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.
PubMed 39213194
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HELIOS-B: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
- ClinicalTrials.gov ID
- NCT04153149
- Acronym / sponsor ID
- ALN-TTRSC02-003
- Keywords
- ATTR, Cardiomyopathy, Amyloidosis, TTR, Transthyretin, TTR-mediated amyloidosis, Amyloidosis, Hereditary, Amyloidosis, Hereditary, Transthyretin-Related
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 655 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 26 Nov 2019 (actual)
- Primary completion
- 8 May 2024 (actual)
- Study completion
- 13 Jan 2027 (estimated)
- First posted
- 6 Nov 2019 (actual)
- Results
- Posted 21 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vutrisiran 25 mg | Experimental | Drug: VutrisiranParticipants 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. |
| Placebo | Placebo comparator | Drug: Vutrisiran, Drug: Sterile Normal Saline (0.9% NaCl)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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VutrisiranAlso: ALN-TTRSC02Vutrisiran will be administered by SC injection. | Drug | Placebo, Vutrisiran 25 mg |
| Sterile Normal Saline (0.9% NaCl)Sterile normal saline (0.9% NaCl) will be administered by SC injection. | Drug | Placebo |
Primary outcome
Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) in the Overall Population
Time frame: Up to Month 36
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) were compared between treatment groups using a modified Andersen-Gill model with a robust variance. All-cause mortality included heart transplantation and LVAD placement events along with deaths; recurrent CV events included CV hospitalizations and urgent HF visits. The number of participants with at least one CV event or all-cause mortality event have been reported here. No imputation was done for participants who dropped out early for the primary analysis of this composite outcome endpoint.
Composite Endpoint of All-Cause Mortality and Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) in the Vutrisiran Monotherapy Subgroup
Time frame: Up to Month 36
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) were compared between treatment groups using a modified Andersen-Gill model with a robust variance. All-cause mortality included heart transplantation and LVAD placement events along with deaths; recurrent CV events included CV hospitalizations and urgent HF visits. The number of participants with at least one CV event or all-cause mortality event have been reported here. No imputation was done for participants who dropped out early for the primary analysis of this composite outcome endpoint.
7 secondary outcomes
Change From Baseline in 6-Minute Walk Test (6-MWT) in the Overall Population
Time frame: Baseline to Month 30
Change From Baseline in 6-MWT in the Vutrisiran Monotherapy Subgroup
Time frame: Baseline to Month 30
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score in the Overall Population
Time frame: Baseline to Month 30
Change From Baseline in the KCCQ-OS Score in the Vutrisiran Monotherapy Subgroup
Time frame: Baseline to Month 30
All-cause Mortality in the Overall Population and Vutrisiran Monotherapy Subgroup
Time frame: Up to 42 months
Percentage of Participants With Change in NYHA Class at Month 30 in the Overall Population
Time frame: Baseline to Month 30
Percentage of Participants With Change in NYHA Class at Month 30 in the Vutrisiran Monotherapy Subgroup
Time frame: Baseline to Month 30
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42669070Hamatani Y, Claggett BL, Cuddy SAM, Sarswat N, Vaishnav J, Grogan M, Maurer MS, Witteles RM, Gonzalez-Lopez E, Garcia-Pavia P, Sheikh FH, Drachman BM, Kosheleff A, Bansilal S, Gillmore JD, Fontana M, Solomon SD. Effect of Vutrisiran According to Baseline Tafamidis Use in Transthyretin Amyloidosis With Cardiomyopathy: Insights From HELIOS-B. J Am Coll Cardiol. 2026 Aug 30:S0735-1097(26)07208-6. doi: 10.1016/j.jacc.2026.07.022. Online ahead of print.
- Derived from this study: PubMed 42669069Abovich A, Fontana M, Claggett B, Gillmore JD, Cappelli F, Ambardekar AV, Morbach C, Garcia-Pavia P, Witteles RM, Maurer MS, Jay PY, Kosheleff A, Bansilal S, Solomon SD. Influence of Disease-Modifying Therapy on the Efficacy of Vutrisiran in Transthyretin Cardiac Amyloidosis. J Am Coll Cardiol. 2026 Aug 5:S0735-1097(26)07209-8. doi: 10.1016/j.jacc.2026.07.023. Online ahead of print.
- Derived from this study: PubMed 42669065Gillmore JD, Hamatani Y, Fontana M, Vaduganathan M, Claggett BL, Garcia-Pavia P, Masri A, Cappelli F, Grogan M, Morbach C, Maurer MS, Solomon SD. Gene Silencer Therapy in Transthyretin Amyloid Cardiomyopathy: A Meta-Analysis of Outcomes Trials. JAMA. 2026 Aug 30. doi: 10.1001/jama.2026.17246. Online ahead of print.
- Derived from this study: PubMed 42646924Jering KS, Manafi A, Claggett BL, Fontana M, Gillmore JD, Bulwer BE, Roshanali F, Prasad N, Jay PY, Solomon SD, Skali H. Right Ventricular Function, Clinical Outcomes, and Effect of Vutrisiran in Transthyretin Amyloidosis With Cardiomyopathy: Secondary Analysis of the HELIOS-B Randomized Clinical Trial. JAMA Cardiol. 2026 Aug 26. doi: 10.1001/jamacardio.2026.3390. Online ahead of print.
- Derived from this study: PubMed 42616515Jering KS, Manafi A, Claggett BL, Bart NK, Prasad N, Birkhoelzer SM, Hamatani Y, Lairez O, Tsujita K, Gillmore JD, Maurer MS, Jay PY, Skali H, Fontana M, Solomon SD. Left Atrial Structure and Function, Clinical Outcomes, and Efficacy of Vutrisiran in Transthyretin Amyloidosis With Cardiomyopathy: A Secondary Analysis of the HELIOS-B Randomized Clinical Trial. JAMA Cardiol. 2026 Aug 19:e262992. doi: 10.1001/jamacardio.2026.2992. Online ahead of print.
- Derived from this study: PubMed 42201475Fontana M, Algalarrondo V, Garcia-Pavia P, Maurer MS, Gillmore JD, Cappelli F, Kolachana K, Gao X, Jadhav S, Mehrotra N, Robbie G, Badri P. Vutrisiran-Mediated Knockdown of Transthyretin in Patients with ATTR Amyloidosis. Clin Pharmacokinet. 2026 Jul;65(7):1073-1085. doi: 10.1007/s40262-026-01651-3. Epub 2026 May 27.
- Derived from this study: PubMed 42165759Endo J, Minamino T, Oh J, Tahara N, Tsujita K, Izumi C, Okumura T, Onoue K, Kitaoka H, Chen C, Chan-Daniels A, Kim D. Vutrisiran in East Asian Patients With Transthyretin Amyloidosis With Cardiomyopathy: Post-Hoc Analysis of HELIOS-B. JACC Asia. 2026 Aug;6(8 Pt 1):1517-1527. doi: 10.1016/j.jacasi.2026.03.031. Epub 2026 May 21.
- Derived from this study: PubMed 41225306Claggett BL, Fontana M, Vaduganathan M, Hamatani Y, Maurer MS, Gillmore JD, Solomon SD. Timing of Mortality Benefit in Outcomes Trials in Transthyretin Amyloidosis. J Am Coll Cardiol. 2026 Feb 10;87(5):522-529. doi: 10.1016/j.jacc.2025.09.1512. Epub 2025 Sep 25.
- Derived from this study: PubMed 40770082Jering 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.
- Derived from this study: PubMed 40769675Maurer 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.
- Derived from this study: PubMed 40380962Witteles 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.
- Derived from this study: PubMed 40099776Maurer 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Alnylam Pharmaceuticals
121 sites in 33 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vutrisiran and Sterile Normal Saline (0.9% NaCl) in people with Transthyretin Amyloidosis (ATTR) With Cardiomyopathy, run by Alnylam Pharmaceuticals at 121 sites in 33 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 121 sites in United States, Japan, United Kingdom, Germany, Poland and 28 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) in the Overall Population (time frame: Up to Month 36). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04153149, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.