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

Alnylam Pharmaceuticals

Status and phase: Active, not recruiting; Phase 3

Conditions: Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

Treatments: Drug: Vutrisiran; Drug: Sterile Normal Saline (0.9% NaCl)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04153149

2019-003153-28 (EudraCT Number)

ALN-TTRSC02-003

2023-508366-15 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 655 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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655 participants in 2 patient groups, including a placebo group

Vutrisiran 25 mg

Experimental group

Description:

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.

Treatment:

Drug: Vutrisiran

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Sterile Normal Saline (0.9% NaCl)

Drug: Vutrisiran