Clinical trial NCT04153149: HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
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
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-11-06
Enrollment: 655
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) in the Overall Population
timeFrame: Up to Month 36
measure: Composite Endpoint of All-Cause Mortality and Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) in the Vutrisiran Monotherapy Subgroup
timeFrame: Up to Month 36
Secondary outcomes:
measure: Change from Baseline in 6-Minute Walk Test (6-MWT) in the Overall Population and Vutrisiran Monotherapy Subgroup
timeFrame: Baseline to Month 30
measure: Change from Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) in the Overall Population and Vutrisiran Monotherapy Subgroup
timeFrame: Baseline to Month 30
measure: All-cause Mortality in the Overall Population and Vutrisiran Monotherapy Subgroup
timeFrame: Up to 42 months
measure: Change from Baseline in New York Heart Association (NYHA) Class in the Overall Population and Vutrisiran Monotherapy Subgroup
timeFrame: Baseline to Month 30
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Clinical Trial Site
state: California
city: Washington
country: United States
facility: Clinical Trial Site
state: District of Columbia
city: Gainesville
country: United States
facility: Clinical Trial Site
state: Georgia
city: Evanston
country: United States
facility: Clinical Trial Site
state: Illinois
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Rochester
country: United States
facility: Clinical Trial Site
state: Minnesota
city: Manhasset
country: United States
facility: Clinical Trial Site
state: New York
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Durham
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Cleveland
country: United States
facility: Clinical Trial Site
state: Ohio
city: Philadelphia
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: Buenos Aires
country: Argentina
facility: Clinical Trial Site
city: Adelaide
country: Australia
facility: Clinical Trial Site
city: Melbourne
country: Australia
facility: Clinical Trial Site
city: Sydney
country: Australia
facility: Clinical Trial Site
city: Westmead
country: Australia
facility: Clinical Trial Site
city: Woolloongabba
country: Australia
facility: Clinical Trial Site
city: Vienna
country: Austria
facility: Clinical Trial Site
city: Anderlecht
country: Belgium
facility: Clinical Trial Site
city: Dendermonde
country: Belgium
facility: Clinical Trial Site
city: Ghent
country: Belgium
facility: Clinical Trial Site
city: Leuven
country: Belgium
facility: Clinical Trial Site
city: Quebec City
country: Canada
facility: Clinical Trial Site
city: Toronto
country: Canada
facility: Clinical Trial Site
city: Zagreb
country: Croatia
facility: Clinical Trial Site
city: Olomouc
country: Czechia
facility: Clinical Trial Site
city: Prague
country: Czechia
facility: Clinical Trial Site
city: Aarhus
country: Denmark
facility: Clinical Trial Site
city: Odense
country: Denmark
facility: Clinical Trial Site
city: Créteil
country: France
facility: Clinical Trial Site
city: Marseille
country: France
facility: Clinical Trial Site
city: Paris
country: France
facility: Clinical Trial Site
city: Toulouse
country: France
facility: Clinical Trial Site
city: Essen
country: Germany
facility: Clinical Trial Site
city: Göttingen
country: Germany
facility: Clinical Trial Site
city: Heidelberg
country: Germany
facility: Clinical Trial Site
city: Leipzig
country: Germany
facility: Clinical Trial Site
city: Münster
country: Germany
facility: Clinical Trial Site
city: Würzburg
country: Germany
facility: Clinical Trial Site
city: Budapest
country: Hungary
facility: Clinical Trial Site
city: Dublin
country: Ireland
facility: Clinical Trial Site
city: Haifa
country: Israel
facility: Clinical Trial Site
city: Aichi
country: Japan
facility: Clinical Trial Site
city: Fukuoka
country: Japan
facility: Clinical Trial Site
city: Kagawa
country: Japan
facility: Clinical Trial Site
city: Kashihara
country: Japan
facility: Clinical Trial Site
city: Kumamoto
country: Japan
facility: Clinical Trial Site
city: Matsumoto
country: Japan
facility: Clinical Trial Site
city: Nankoku
country: Japan
facility: Clinical Trial Site
city: Osaka
country: Japan
facility: Clinical Trial Site
city: Tokyo
country: Japan
facility: Clinical Trial Site
city: Seoul
country: Korea, Republic of
facility: Clinical Trial Site
city: Riga
country: Latvia
facility: Clinical Trial Site
city: Kaunas
country: Lithuania
facility: Clinical Trial Site
city: Groningen
country: Netherlands
facility: Clinical Trial Site
city: Utrecht
country: Netherlands
facility: Clinical Trial Site
city: Oslo
country: Norway
facility: Clinical Trial Site
city: Lima
country: Peru
facility: Clinical Trial Site
city: San Miguel
country: Peru
facility: Clinical Trial Site
city: Gdańsk
country: Poland
facility: Clinical Trial Site
city: Wrocław
country: Poland
facility: Clinical Trial Site
city: Guimarães
country: Portugal
facility: Clinical Trial Site
city: Lisboa
country: Portugal
facility: Clinical Trial Site
city: Porto
country: Portugal
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Bilbao
country: Spain
facility: Clinical Trial Site
city: Huelva
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Málaga
country: Spain
facility: Clinical Trial Site
city: Gothenburg
country: Sweden
facility: Clinical Trial Site
city: Umeå
country: Sweden
facility: Clinical Trial Site
city: Birmingham
country: United Kingdom
facility: Clinical Trial Site
city: Cardiff
country: United Kingdom
facility: Clinical Trial Site
city: Glasgow
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
city: Manchester
country: United Kingdom
facility: Clinical Trial Site
city: Middlesbrough
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: