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

Study Overview
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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 patients with ATTR amyloidosis with cardiomyopathy.

Official Title
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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)

Conditions
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Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

Intervention / Treatment
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* Drug: Vutrisiran
* Drug: Sterile Normal Saline (0.9% NaCl)


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vutrisiran 25 mg<br>Participants will receive vutrisiran 25 mg administered subcutaneously (SC) once every 3 months (q3M) during the double-blind period. | Drug: Vutrisiran<br>* Vutrisiran 25 mg will be administered by SC injection q3M.<br>* Other names: ALN-TTRSC02;|
| Placebo Comparator: Placebo<br>Participants will receive placebo during the double-blind period. | Drug: Sterile Normal Saline (0.9% NaCl)<br>* Sterile normal saline (0.9% NaCl) will be administered by SC injection q3M.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) | All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) will be compared between treatment groups using an Andersen-Gill model. | 30-36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in 6-Minute Walk Test (6-MWT) at Month 30 |  | Baseline, Month 30 | 
| Change from Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) at Month 30 | The KCCQ is a 23-item self-administered questionnaire quantifying 6 domains (symptoms, physical function, quality of life, social limitation, self-efficacy, and symptom stability) and 2 summary scores (clinical and overall summary [OS]). Scores are transformed to a range of 0-100, in which higher scores reflect better health status. | Baseline, Month 30 | 
| Change from Baseline in Mean Left Ventricular (LV) Wall Thickness by Echocardiographic Assessment at Month 30 |  | Baseline, Month 30 | 
| Change from Baseline in Global Longitudinal Strain by Echocardiographic Assessment at Month 30 |  | Baseline and Month 30 | 
| Composite Endpoint of All-Cause Mortality and Recurrent All-cause Hospitalizations and Urgent HF Visits | All-cause mortality and recurrent all-cause hospitalizations and urgent HF visits will be compared between treatment groups using an Andersen-Gill model. | 30-36 months | 
| All-cause Mortality |  | 30-36 months | 
| Rate of Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) |  | 30-36 months | 
| Change from Baseline in N-terminal prohormone B-type Natriuretic Peptide (NTproBNP) at Month 30 |  | Baseline, Month 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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