Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
Conditions
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
Brief 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.
Interventions
DRUGVutrisiran
Vutrisiran will be administered by SC injection.
DRUGSterile Normal Saline (0.9% NaCl)
Sterile normal saline (0.9% NaCl) will be administered by SC injection.
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
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, United States
Participant flow
Recruitment details
A total of 655 participants with hereditary amyloid transthyretin (hATTR) amyloidosis or wild-type ATTR (wtATTR) amyloidosis with cardiomyopathy took part in the study at 87 sites across 26 countries in North America, South America, Europe, Asia, and Australia. This study is still ongoing.
Pre-assignment details
The study consists of 2 parts: Double-blind (DB) Period and Open-label Treatment Extension (OLE) Period. In the DB period, participants were randomized in a 1:1 ratio to receive vutrisiran or placebo and during the OLE Period, all participants receive vutrisiran. The DB period of the study has been completed while OLE period is still ongoing.
Participants by arm
| Arm | Count |
|---|---|
| DB Period: Placebo Participants in the DB period received vutrisiran matching placebo, SC injection, q3M for up to 36 months. | 328 |
| DB Period: Vutrisiran Participants in the DB period received vutrisiran, 25 mg, SC injection, q3M for up to 36 months. | 326 |
| Total | 654 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double Blind Period | Adverse Event | 6 | 2 | 0 | 0 |
| Double Blind Period | Death | 63 | 49 | 0 | 0 |
| Double Blind Period | Lost to Follow-up | 2 | 1 | 0 | 0 |
| Double Blind Period | Physician Decision | 2 | 0 | 0 | 0 |
| Double Blind Period | Reason Not Specified | 5 | 4 | 0 | 0 |
| Double Blind Period | Withdrawal by guardian | 0 | 2 | 0 | 0 |
| Double Blind Period | Withdrawal by Subject | 16 | 11 | 0 | 0 |
| Open Label Extension Period | Death | 0 | 0 | 7 | 3 |
| Open Label Extension Period | Participant Withdrew from Treatment but Ongoing in Safety Follow-up | 0 | 0 | 0 | 1 |
| Open Label Extension Period | Study Treatment Ongoing | 0 | 0 | 213 | 237 |
| Open Label Extension Period | Withdrawal by guardian | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | DB Period: Placebo | DB Period: Vutrisiran | Total |
|---|---|---|---|
| Age, Continuous | 75.2 years STANDARD_DEVIATION 6.3 | 75.5 years STANDARD_DEVIATION 7.2 | 75.4 years STANDARD_DEVIATION 6.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 22 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 304 Participants | 298 Participants | 602 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 6 Participants | 14 Participants |
| Race/Ethnicity, Customized Asian | 19 Participants | 18 Participants | 37 Participants |
| Race/Ethnicity, Customized Black or African American | 24 Participants | 23 Participants | 47 Participants |
| Race/Ethnicity, Customized Not reported | 8 Participants | 6 Participants | 14 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 275 Participants | 277 Participants | 552 Participants |
| Sex: Female, Male Female | 22 Participants | 27 Participants | 49 Participants |
| Sex: Female, Male Male | 306 Participants | 299 Participants | 605 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 63 / 328 | 49 / 326 |
| other Total, other adverse events | 303 / 328 | 293 / 326 |
| serious Total, serious adverse events | 220 / 328 | 201 / 326 |
Outcome results
Primary
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.
Time frame: Up to Month 36
Population: FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 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 | 159 Participants |
| DB Period: Vutrisiran | Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) in the Overall Population | 125 Participants |
Comparison: Analysis done using a modified Andersen-Gill model with a robust variance. The model included treatment group, ATTR amyloidosis disease type, New York Heart Association (NYHA) class, age group, and log-transformed baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) as covariates.p-value: =0.011895% CI: [0.555, 0.929]Modified Andersen-Gill Model
Primary
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.
Time frame: Up to Month 36
Population: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DB Period: Placebo | Composite Endpoint of All-Cause Mortality and Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) in the Vutrisiran Monotherapy Subgroup | 105 Participants |
| DB Period: Vutrisiran | Composite Endpoint of All-Cause Mortality and Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) in the Vutrisiran Monotherapy Subgroup | 76 Participants |
Comparison: Analysis done using a modified Andersen-Gill model with a robust variance. The model included treatment group, ATTR amyloidosis disease type, NYHA class, age group, and log-transformed baseline NT-proBNP as covariates.p-value: =0.016295% CI: [0.487, 0.929]Modified Andersen-Gill Model
Secondary
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.
Time frame: Up to 42 months
Secondary
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).
Time frame: Baseline to Month 30
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo | Change From Baseline in 6-Minute Walk Test (6-MWT) in the Overall Population | -71.88 meters | Standard Error 4.79 |
| DB Period: Vutrisiran | Change From Baseline in 6-Minute Walk Test (6-MWT) in the Overall Population | -45.42 meters | Standard Error 4.62 |
Comparison: Analysis done using MMRM with baseline 6-MWT as a covariate and fixed effect terms including treatment group, visit, treatment-by-visit interaction, baseline tafamidis use, treatment-by-baseline tafamidis use interaction, type of ATTR amyloidosis, and age group. 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.p-value: =0.000079795% CI: [13.38, 39.55]MMRM
Secondary
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.
Time frame: Baseline to Month 30
Population: 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).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo | Change From Baseline in 6-MWT in the Vutrisiran Monotherapy Subgroup | -91.78 meters | Standard Error 6.39 |
| DB Period: Vutrisiran | Change From Baseline in 6-MWT in the Vutrisiran Monotherapy Subgroup | -59.69 meters | Standard Error 6.6 |
Comparison: Analysis done using MMRM with baseline 6-MWT as a covariate and fixed effect terms including treatment group, visit, treatment-by-visit interaction, type of ATTR amyloidosis, and age group. 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.p-value: =0.000595% CI: [14.03, 50.15]MMRM
Secondary
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.
Time frame: Baseline to Month 30
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo | Change From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score in the Overall Population | -15.49 score on a scale | Standard Error 1.26 |
| DB Period: Vutrisiran | Change From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score in the Overall Population | -9.68 score on a scale | Standard Error 1.19 |
Comparison: Analysis done using MMRM with baseline KCCQ-OS as a covariate and fixed effect terms including treatment group, visit, treatment-by-visit interaction, baseline tafamidis use, treatment-by-baseline tafamidis use interaction, type of ATTR amyloidosis, and age group. Missing change values due to death were imputed using sampling with replacement from the worst 10% of observed values, as specified in the SAP.p-value: =0.000895% CI: [2.4, 9.2]MMRM
Secondary
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.
Time frame: Baseline to Month 30
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DB Period: Placebo | Change From Baseline in the KCCQ-OS Score in the Vutrisiran Monotherapy Subgroup | -19.47 score on a scale | Standard Error 1.73 |
| DB Period: Vutrisiran | Change From Baseline in the KCCQ-OS Score in the Vutrisiran Monotherapy Subgroup | -10.78 score on a scale | Standard Error 1.66 |
Comparison: Analysis done using MMRM with baseline KCCQ-OS as a covariate and fixed effect terms including treatment group, visit, treatment-by-visit interaction, type of ATTR amyloidosis, and age group. Missing change values due to death were imputed using sampling with replacement from the worst 10% of observed values, as specified in the SAP.p-value: =0.000395% CI: [3.98, 13.4]MMRM
Secondary
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: 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.
Time frame: Baseline to Month 30
Population: FAS included all participants who were randomized and received any amount of study drug (vutrisiran or placebo).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DB Period: Placebo | Percentage of Participants With Change in NYHA Class at Month 30 in the Overall Population | Stable or improved from baseline | 60.5 percentage of participants |
| DB Period: Placebo | Percentage of Participants With Change in NYHA Class at Month 30 in the Overall Population | Worsened from baseline | 39.5 percentage of participants |
| DB Period: Vutrisiran | Percentage of Participants With Change in NYHA Class at Month 30 in the Overall Population | Stable or improved from baseline | 67.8 percentage of participants |
| DB Period: Vutrisiran | Percentage of Participants With Change in NYHA Class at Month 30 in the Overall Population | Worsened from baseline | 32.2 percentage of participants |
p-value: =0.021795% CI: [1.3, 16.1]Cochran-Mantel-Haenszel
Secondary
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: 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.
Time frame: Baseline to Month 30
Population: Vutrisiran Monotherapy Subgroup FAS included all participants who were not on tafamidis at the study baseline in the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DB Period: Placebo | Percentage of Participants With Change in NYHA Class at Month 30 in the Vutrisiran Monotherapy Subgroup | Stable or improved from baseline | 56.4 percentage of participants |
| DB Period: Placebo | Percentage of Participants With Change in NYHA Class at Month 30 in the Vutrisiran Monotherapy Subgroup | Worsened from baseline | 43.6 percentage of participants |
| DB Period: Vutrisiran | Percentage of Participants With Change in NYHA Class at Month 30 in the Vutrisiran Monotherapy Subgroup | Stable or improved from baseline | 66.3 percentage of participants |
| DB Period: Vutrisiran | Percentage of Participants With Change in NYHA Class at Month 30 in the Vutrisiran Monotherapy Subgroup | Worsened from baseline | 33.7 percentage of participants |
p-value: =0.012195% CI: [2.7, 22.2]Cochran-Mantel-Haenszel