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

NCT04153149, Phase 3, Active not recruiting, Alnylam Pharmaceuticals; results first posted 2025-10-21

Trial 11

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Field	Value	Source
Title	HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy	ClinicalTrials.gov
NCT number	NCT04153149	ClinicalTrials.gov
Status	Active not recruiting	ClinicalTrials.gov
Phases	Phase 3	ClinicalTrials.gov
Enrollment	655 participants, actual	ClinicalTrials.gov
Lead sponsor	Alnylam Pharmaceuticals	ClinicalTrials.gov
Conditions	Transthyretin Amyloidosis (ATTR) With Cardiomyopathy	ClinicalTrials.gov
Interventions	Vutrisiran, Sterile Normal Saline (0.9% NaCl)	ClinicalTrials.gov
First posted	2019-11-06	ClinicalTrials.gov
Last updated	2026-11-02	ClinicalTrials.gov
Results first posted	2025-10-21	ClinicalTrials.gov

Registered outcomes 9

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description	Source
Primary	Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) in the Overall Population	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.	ClinicalTrials.gov
Primary	Composite Endpoint of All-Cause Mortality and Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) in the Vutrisiran Monotherapy Subgroup	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.	ClinicalTrials.gov
Secondary	Change From Baseline in 6-Minute Walk Test (6-MWT) in the Overall Population	Baseline to Month 30	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).	ClinicalTrials.gov
Secondary	Change From Baseline in 6-MWT in the Vutrisiran Monotherapy Subgroup	Baseline to Month 30	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.	ClinicalTrials.gov
Secondary	Change From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score in the Overall Population	Baseline to Month 30	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.	ClinicalTrials.gov
Secondary	Change From Baseline in the KCCQ-OS Score in the Vutrisiran Monotherapy Subgroup	Baseline to Month 30	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.	ClinicalTrials.gov
Secondary	All-cause Mortality in the Overall Population and Vutrisiran Monotherapy Subgroup	Up to 42 months	All-cause mortality also included heart transplantation and LVAD placement events along with deaths; recurrent CV events included CV hospitalizations and urgent HF visits.	ClinicalTrials.gov
Secondary	Percentage of Participants With Change in NYHA Class at Month 30 in the Overall Population	Baseline to Month 30	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: 1\) 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.	ClinicalTrials.gov
Secondary	Percentage of Participants With Change in NYHA Class at Month 30 in the Vutrisiran Monotherapy Subgroup	Baseline to Month 30	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: 1\) 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.	ClinicalTrials.gov

Outcomes 9

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as	Source
PRIMARY	Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) in the Overall Population	Up to Month 36	FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo).	Participants	COUNT_OF_PARTICIPANTS	ClinicalTrials.gov
PRIMARY	Composite Endpoint of All-Cause Mortality and Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) in the Vutrisiran Monotherapy Subgroup	Up to Month 36	Vutrisiran Monotherapy Subgroup FAS included all participants who were not on tafamidis at the study baseline in the FAS. FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo).	Participants	COUNT_OF_PARTICIPANTS	ClinicalTrials.gov
SECONDARY	Change From Baseline in 6-Minute Walk Test (6-MWT) in the Overall Population	Baseline to Month 30	FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo). Overall number analyzed is the number of participants with data available for analysis.	meters	LEAST_SQUARES_MEAN	ClinicalTrials.gov
SECONDARY	Change From Baseline in 6-MWT in the Vutrisiran Monotherapy Subgroup	Baseline to Month 30	Vutrisiran Monotherapy Subgroup FAS included all participants who were not on tafamidis at the study baseline in the FAS. FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo).	meters	LEAST_SQUARES_MEAN	ClinicalTrials.gov
SECONDARY	Change From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score in the Overall Population	Baseline to Month 30	FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo). Overall number analyzed is the number of participants with data available for analysis.	score on a scale	LEAST_SQUARES_MEAN	ClinicalTrials.gov
SECONDARY	Change From Baseline in the KCCQ-OS Score in the Vutrisiran Monotherapy Subgroup	Baseline to Month 30	Vutrisiran Monotherapy Subgroup FAS included all participants who were not on tafamidis at the study baseline in the FAS. Overall number analyzed is the number of participants with data available for analysis.	score on a scale	LEAST_SQUARES_MEAN	ClinicalTrials.gov
SECONDARY	All-cause Mortality in the Overall Population and Vutrisiran Monotherapy Subgroup	Up to 42 months				ClinicalTrials.gov
SECONDARY	Percentage of Participants With Change in NYHA Class at Month 30 in the Overall Population	Baseline to Month 30	FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo).	percentage of participants	NUMBER	ClinicalTrials.gov
SECONDARY	Percentage of Participants With Change in NYHA Class at Month 30 in the Vutrisiran Monotherapy Subgroup	Baseline to Month 30	Vutrisiran Monotherapy Subgroup FAS included all participants who were not on tafamidis at the study baseline in the FAS.	percentage of participants	NUMBER	ClinicalTrials.gov

Results by group 20

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units	Source
Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) in the Overall Population	DB Period: Placebo		159		Participants	ClinicalTrials.gov
Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) in the Overall Population	DB Period: Vutrisiran		125		Participants	ClinicalTrials.gov
Composite Endpoint of All-Cause Mortality and Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) in the Vutrisiran Monotherapy Subgroup	DB Period: Placebo		105		Participants	ClinicalTrials.gov
Composite Endpoint of All-Cause Mortality and Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) in the Vutrisiran Monotherapy Subgroup	DB Period: Vutrisiran		76		Participants	ClinicalTrials.gov
Change From Baseline in 6-Minute Walk Test (6-MWT) in the Overall Population	DB Period: Placebo		-71.88	Standard Error 4.79	meters	ClinicalTrials.gov
Change From Baseline in 6-Minute Walk Test (6-MWT) in the Overall Population	DB Period: Vutrisiran		-45.42	Standard Error 4.62	meters	ClinicalTrials.gov
Change From Baseline in 6-MWT in the Vutrisiran Monotherapy Subgroup	DB Period: Placebo		-91.78	Standard Error 6.39	meters	ClinicalTrials.gov
Change From Baseline in 6-MWT in the Vutrisiran Monotherapy Subgroup	DB Period: Vutrisiran		-59.69	Standard Error 6.60	meters	ClinicalTrials.gov
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score in the Overall Population	DB Period: Placebo		-15.49	Standard Error 1.26	score on a scale	ClinicalTrials.gov
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score in the Overall Population	DB Period: Vutrisiran		-9.68	Standard Error 1.19	score on a scale	ClinicalTrials.gov
Change From Baseline in the KCCQ-OS Score in the Vutrisiran Monotherapy Subgroup	DB Period: Placebo		-19.47	Standard Error 1.73	score on a scale	ClinicalTrials.gov
Change From Baseline in the KCCQ-OS Score in the Vutrisiran Monotherapy Subgroup	DB Period: Vutrisiran		-10.78	Standard Error 1.66	score on a scale	ClinicalTrials.gov
Percentage of Participants With Change in NYHA Class at Month 30 in the Overall Population	DB Period: Placebo	Stable or improved from baseline	60.5		percentage of participants	ClinicalTrials.gov
Percentage of Participants With Change in NYHA Class at Month 30 in the Overall Population	DB Period: Vutrisiran	Stable or improved from baseline	67.8		percentage of participants	ClinicalTrials.gov
Percentage of Participants With Change in NYHA Class at Month 30 in the Overall Population	DB Period: Placebo	Worsened from baseline	39.5		percentage of participants	ClinicalTrials.gov
Percentage of Participants With Change in NYHA Class at Month 30 in the Overall Population	DB Period: Vutrisiran	Worsened from baseline	32.2		percentage of participants	ClinicalTrials.gov
Percentage of Participants With Change in NYHA Class at Month 30 in the Vutrisiran Monotherapy Subgroup	DB Period: Placebo	Stable or improved from baseline	56.4		percentage of participants	ClinicalTrials.gov
Percentage of Participants With Change in NYHA Class at Month 30 in the Vutrisiran Monotherapy Subgroup	DB Period: Vutrisiran	Stable or improved from baseline	66.3		percentage of participants	ClinicalTrials.gov
Percentage of Participants With Change in NYHA Class at Month 30 in the Vutrisiran Monotherapy Subgroup	DB Period: Placebo	Worsened from baseline	43.6		percentage of participants	ClinicalTrials.gov
Percentage of Participants With Change in NYHA Class at Month 30 in the Vutrisiran Monotherapy Subgroup	DB Period: Vutrisiran	Worsened from baseline	33.7		percentage of participants	ClinicalTrials.gov

Participant flow 24

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants	Source
Double Blind Period	STARTED	DB Period: Placebo	329	ClinicalTrials.gov
Double Blind Period	STARTED	DB Period: Vutrisiran	326	ClinicalTrials.gov
Double Blind Period	STARTED	OLE Period: Placebo/Vutrisiran	0	ClinicalTrials.gov
Double Blind Period	STARTED	OLE Period: Vutrisiran/Vutrisiran	0	ClinicalTrials.gov
Double Blind Period	COMPLETED	DB Period: Placebo	235	ClinicalTrials.gov
Double Blind Period	COMPLETED	DB Period: Vutrisiran	257	ClinicalTrials.gov
Double Blind Period	COMPLETED	OLE Period: Placebo/Vutrisiran	0	ClinicalTrials.gov
Double Blind Period	COMPLETED	OLE Period: Vutrisiran/Vutrisiran	0	ClinicalTrials.gov
Double Blind Period	NOT COMPLETED	DB Period: Placebo	94	ClinicalTrials.gov
Double Blind Period	NOT COMPLETED	DB Period: Vutrisiran	69	ClinicalTrials.gov
Double Blind Period	NOT COMPLETED	OLE Period: Placebo/Vutrisiran	0	ClinicalTrials.gov
Double Blind Period	NOT COMPLETED	OLE Period: Vutrisiran/Vutrisiran	0	ClinicalTrials.gov
Open Label Extension Period	STARTED	DB Period: Placebo	0	ClinicalTrials.gov
Open Label Extension Period	STARTED	DB Period: Vutrisiran	0	ClinicalTrials.gov
Open Label Extension Period	STARTED	OLE Period: Placebo/Vutrisiran	221	ClinicalTrials.gov
Open Label Extension Period	STARTED	OLE Period: Vutrisiran/Vutrisiran	241	ClinicalTrials.gov
Open Label Extension Period	COMPLETED	DB Period: Placebo	0	ClinicalTrials.gov
Open Label Extension Period	COMPLETED	DB Period: Vutrisiran	0	ClinicalTrials.gov
Open Label Extension Period	COMPLETED	OLE Period: Placebo/Vutrisiran	0	ClinicalTrials.gov
Open Label Extension Period	COMPLETED	OLE Period: Vutrisiran/Vutrisiran	0	ClinicalTrials.gov

Adverse events 846

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events	Source
other	Anaemia	Blood and lymphatic system disorders	DB Period: Placebo	16	328	16	ClinicalTrials.gov
other	Anaemia	Blood and lymphatic system disorders	DB Period: Vutrisiran	19	326	20	ClinicalTrials.gov
other	Atrial fibrillation	Cardiac disorders	DB Period: Placebo	58	328	65	ClinicalTrials.gov
other	Atrial fibrillation	Cardiac disorders	DB Period: Vutrisiran	59	326	78	ClinicalTrials.gov
other	Atrial flutter	Cardiac disorders	DB Period: Placebo	17	328	21	ClinicalTrials.gov
other	Atrial flutter	Cardiac disorders	DB Period: Vutrisiran	24	326	26	ClinicalTrials.gov
other	Cardiac failure	Cardiac disorders	DB Period: Placebo	105	328	161	ClinicalTrials.gov
other	Cardiac failure	Cardiac disorders	DB Period: Vutrisiran	79	326	103	ClinicalTrials.gov
other	Cardiac failure congestive	Cardiac disorders	DB Period: Placebo	17	328	18	ClinicalTrials.gov
other	Cardiac failure congestive	Cardiac disorders	DB Period: Vutrisiran	8	326	9	ClinicalTrials.gov
other	Palpitations	Cardiac disorders	DB Period: Placebo	18	328	18	ClinicalTrials.gov
other	Palpitations	Cardiac disorders	DB Period: Vutrisiran	4	326	4	ClinicalTrials.gov
other	Hypothyroidism	Endocrine disorders	DB Period: Placebo	17	328	17	ClinicalTrials.gov
other	Hypothyroidism	Endocrine disorders	DB Period: Vutrisiran	11	326	11	ClinicalTrials.gov
other	Constipation	Gastrointestinal disorders	DB Period: Placebo	42	328	53	ClinicalTrials.gov
other	Constipation	Gastrointestinal disorders	DB Period: Vutrisiran	33	326	35	ClinicalTrials.gov
other	Diarrhoea	Gastrointestinal disorders	DB Period: Placebo	30	328	34	ClinicalTrials.gov
other	Diarrhoea	Gastrointestinal disorders	DB Period: Vutrisiran	15	326	16	ClinicalTrials.gov
other	Nausea	Gastrointestinal disorders	DB Period: Placebo	26	328	28	ClinicalTrials.gov
other	Nausea	Gastrointestinal disorders	DB Period: Vutrisiran	9	326	10	ClinicalTrials.gov

Adverse event totals 6

The totals the trial posted for each group.

Total	Group	Affected	At risk	Source
Total, all-cause mortality	DB Period: Placebo	63	328	ClinicalTrials.gov
Total, all-cause mortality	DB Period: Vutrisiran	49	326	ClinicalTrials.gov
Total, other adverse events	DB Period: Placebo	303	328	ClinicalTrials.gov
Total, other adverse events	DB Period: Vutrisiran	293	326	ClinicalTrials.gov
Total, serious adverse events	DB Period: Placebo	220	328	ClinicalTrials.gov
Total, serious adverse events	DB Period: Vutrisiran	201	326	ClinicalTrials.gov

Papers 15

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
39213194	DERIVED	PubMed
39566871	DERIVED	PubMed
40099776	DERIVED	PubMed
40380962	DERIVED	PubMed
40769675	DERIVED	PubMed
40770082	DERIVED	PubMed
41225306	DERIVED	PubMed
42165759	DERIVED	PubMed
42201475	DERIVED	PubMed
42616515	DERIVED	PubMed
42646924	DERIVED	PubMed
42669065	DERIVED	PubMed
42669069	DERIVED	PubMed
42669070	DERIVED	PubMed
42974684	DERIVED	PubMed

Trial comparisons 4

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison	Source
DB Period: Vutrisiran vs DB Period: Placebo: Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) in the Overall Population	Trial comparisons
DB Period: Vutrisiran vs DB Period: Placebo: Composite Endpoint of All-Cause Mortality and Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) in the Vutrisiran Monotherapy Subgroup	Trial comparisons
DB Period: Vutrisiran vs DB Period: Placebo: deaths from any cause	Trial comparisons
DB Period: Vutrisiran vs DB Period: Placebo: serious adverse events	Trial comparisons

Tests 0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

Test	Named as	Source

Source 4

Field	Value	Source
Release	trials-2026-11-12-0.3.0	ClinicalTrials.gov
Release manifest SHA-256	4a570df2e7274cee2d4fa2959402fab41880e2cd412e4b590390035fbea69391	ClinicalTrials.gov
Registry capture	2026-11-12	ClinicalTrials.gov
Results copy, AACT	2026-03-23	ClinicalTrials.gov

The same record as JSON

Release trials-2026-11-12-0.3.0

ClinicalTrials.gov's posted results, through CTTI's AACT: ClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299 ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

ClinicalTrials.gov: none stated ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.