HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
Phase 3
Active, not recruiting
- Conditions
- Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
- Interventions
- Drug: Sterile Normal Saline (0.9% NaCl)
- Registration Number
- NCT04153149
- Lead Sponsor
- Alnylam Pharmaceuticals
- 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 patients with ATTR amyloidosis with cardiomyopathy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 655
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vutrisiran 25 mg Vutrisiran Participants will receive vutrisiran 25 mg administered subcutaneously (SC) once every 3 months (q3M) during the double-blind (DB) period. After the DB period, participants enter the open-label randomized treatment extension (RTE) period to receive vutrisiran 25 mg SC q3M or vutrisiran 50 mg SC every 6 months (q6M). After implementation of Amendment 4, participants from the DB period will enter the open-label treatment extension (OLE) period to receive vutrisiran 25 mg SC q3M and participants who were previously receiving vutrisiran 50 mg q6M in the RTE period, will be transitioned to vutrisiran 25 mg q3M in the OLE period. Placebo Vutrisiran Participants will receive placebo during the double-blind period. After the DB period, participants enter the RTE period to receive vutrisiran 25 mg SC q3M or vutrisiran 50 mg SC q6M. After implementation of Amendment 4, participants from the DB period will enter the OLE period to receive vutrisiran 25 mg SC q3M and participants who were previously receiving vutrisiran 50 mg q6M in the RTE period, will be transitioned to vutrisiran 25 mg q3M in the OLE period. Placebo Sterile Normal Saline (0.9% NaCl) Participants will receive placebo during the double-blind period. After the DB period, participants enter the RTE period to receive vutrisiran 25 mg SC q3M or vutrisiran 50 mg SC q6M. After implementation of Amendment 4, participants from the DB period will enter the OLE period to receive vutrisiran 25 mg SC q3M and participants who were previously receiving vutrisiran 50 mg q6M in the RTE period, will be transitioned to vutrisiran 25 mg q3M in the OLE period.
- Primary Outcome Measures
Name Time Method 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) will be compared between treatment groups using an Andersen-Gill model. The vutrisiran monotherapy subgroup is defined as the group of participants not on tafamidis at the study baseline.
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) will be compared between treatment groups using an Andersen-Gill model.
- Secondary Outcome Measures
Name Time Method Change from Baseline in 6-Minute Walk Test (6-MWT) in the Overall Population and Vutrisiran Monotherapy Subgroup Baseline to Month 30 Change from Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) in the Overall Population and Vutrisiran Monotherapy Subgroup Baseline to 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.
All-cause Mortality in the Overall Population and Vutrisiran Monotherapy Subgroup Up to 42 months Change from Baseline in New York Heart Association (NYHA) Class in the Overall Population and Vutrisiran Monotherapy Subgroup Baseline to Month 30
Trial Locations
- Locations (1)
Clinical Trial Site
🇬🇧Middlesbrough, United Kingdom