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

Transthyretin Amyloidosis (ATTR) With Cardiomyopathy Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04153149
• Other study ID #: ALN-TTRSC02-003
• Secondary ID: 2019-003153-28
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 26, 2019
• Est. completion date: December 2026

Study information

• Verified date: February 2024
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 655
• Est. completion date: December 2026
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyloid Neuropathies, Familial
• Amyloidosis
• Cardiomyopathies
• Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

Intervention

Drug:
• Vutrisiran
Vutrisiran 25 mg will be administered by SC injection q3M.
• Sterile Normal Saline (0.9% NaCl)
Sterile normal saline (0.9% NaCl) will be administered by SC injection q3M.

Locations

Country	Name	City	State
Argentina	Clinical Trial Site	Buenos Aires
Australia	Clinical Trial Site	Adelaide
Australia	Clinical Trial Site	Melbourne
Australia	Clinical Trial Site	Sydney
Australia	Clinical Trial Site	Westmead
Australia	Clinical Trial Site	Woolloongabba
Austria	Clinical Trial Site	Vienna
Belgium	Clinical Trial Site	Anderlecht
Belgium	Clinical Trial Site	Dendermonde
Belgium	Clinical Trial Site	Ghent
Belgium	Clinical Trial Site	Leuven
Canada	Clinical Trial Site	Quebec City
Canada	Clinical Trial Site	Toronto
Croatia	Clinical Trial Site	Zagreb
Czechia	Clinical Trial Site	Olomouc
Czechia	Clinical Trial Site	Prague
Denmark	Clinical Trial Site	Aarhus
Denmark	Clinical Trial Site	Odense
France	Clinical Trial Site	Créteil
France	Clinical Trial Site	Marseille
France	Clinical Trial Site	Paris
France	Clinical Trial Site	Toulouse
Germany	Clinical Trial Site	Essen
Germany	Clinical Trial Site	Göttingen
Germany	Clinical Trial Site	Heidelberg
Germany	Clinical Trial Site	Leipzig
Germany	Clinical Trial Site	Münster
Germany	Clinical Trial Site	Würzburg
Hungary	Clinical Trial Site	Budapest
Ireland	Clinical Trial Site	Dublin
Israel	Clinical Trial Site	Haifa
Japan	Clinical Trial Site	Aichi
Japan	Clinical Trial Site	Fukuoka
Japan	Clinical Trial Site	Kagawa
Japan	Clinical Trial Site	Kashihara
Japan	Clinical Trial Site	Kumamoto
Japan	Clinical Trial Site	Matsumoto
Japan	Clinical Trial Site	Nankoku
Japan	Clinical Trial Site	Osaka
Japan	Clinical Trial Site	Tokyo
Korea, Republic of	Clinical Trial Site	Seoul
Latvia	Clinical Trial Site	Riga
Lithuania	Clinical Trial Site	Kaunas
Netherlands	Clinical Trial Site	Groningen
Netherlands	Clinical Trial Site	Utrecht
Norway	Clinical Trial Site	Oslo
Peru	Clinical Trial Site	Lima
Peru	Clinical Trial Site	San Miguel
Poland	Clinical Trial Site	Gdansk
Poland	Clinical Trial Site	Wroclaw
Portugal	Clinical Trial Site	Guimarães
Portugal	Clinical Trial Site	Lisboa
Portugal	Clinical Trial Site	Porto
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Bilbao
Spain	Clinical Trial Site	Huelva
Spain	Clinical Trial Site	Madrid
Spain	Clinical Trial Site	Málaga
Sweden	Clinical Trial Site	Gothenburg
Sweden	Clinical Trial Site	Umeå
United Kingdom	Clinical Trial Site	Birmingham
United Kingdom	Clinical Trial Site	Cardiff
United Kingdom	Clinical Trial Site	Glasgow
United Kingdom	Clinical Trial Site	London
United Kingdom	Clinical Trial Site	Manchester
United Kingdom	Clinical Trial Site	Middlesbrough
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Cleveland	Ohio
United States	Clinical Trial Site	Durham	North Carolina
United States	Clinical Trial Site	Evanston	Illinois
United States	Clinical Trial Site	Gainesville	Georgia
United States	Clinical Trial Site	Houston	Texas
United States	Clinical Trial Site	Manhasset	New York
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Philadelphia	Pennsylvania
United States	Clinical Trial Site	Rochester	Minnesota
United States	Clinical Trial Site	Stanford	California
United States	Clinical Trial Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Croatia,  Czechia,  Denmark,  France,  Germany,  Hungary,  Ireland,  Israel,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Netherlands,  Norway,  Peru,  Poland,  Portugal,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change from Baseline in 6-Minute Walk Test (6-MWT) at Month 30		Baseline, Month 30
Secondary	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
Secondary	Change from Baseline in Mean Left Ventricular (LV) Wall Thickness by Echocardiographic Assessment at Month 30		Baseline, Month 30
Secondary	Change from Baseline in Global Longitudinal Strain by Echocardiographic Assessment at Month 30		Baseline and Month 30
Secondary	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
Secondary	All-cause Mortality		30-36 months
Secondary	Rate of Recurrent CV Events (CV Hospitalizations and Urgent HF Visits)		30-36 months
Secondary	Change from Baseline in N-terminal prohormone B-type Natriuretic Peptide (NTproBNP) at Month 30		Baseline, Month 30