Clinical trial NCT02319005: ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)
Official title: A Phase 3 Multicenter, Multinational, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ALN TTRSC in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)
Amyloidosis, Hereditary
Amyloid Neuropathies, Familial
Amyloid Neuropathies
Amyloidosis, Hereditary, Transthyretin-Related
Familial Transthyretin Cardiac Amyloidosis
Keywords: Cardiomyopathy
Heart Failure
FAC
Amyloid
Transthyretin
TTR
RNAi therapeutic
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-12-18
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the safety and efficacy of revusiran (ALN-TTRSC) in patients with transthyretin (TTR) mediated Familial Amyloidotic Cardiomyopathy. Dosing has been discontinued; patients are being followed-up for safety.


Eligibility criteria: Inclusion Criteria:

* Documented TTR mutation
* Amyloid deposits in cardiac or non-cardiac tissue
* Medical history of heart failure
* Evidence of cardiac involvement by echocardiogram

Exclusion Criteria:

* Has known primary amyloidosis (AL), leptomeningeal amyloidosis, non-FAC hereditary cardiomyopathy, hypertensive cardiomyopathy, or cardiomyopathy due to valvular heart disease
* Has known peripheral vascular disease affecting ambulation
* Has a Polyneuropathy Disability score \>2
* Has a New York Heart Association (NYHA) classification of IV

Primary outcomes:
measure: 6 Minute Walk Distance (6-MWD)
timeFrame: 18 months
measure: Serum TTR Levels
timeFrame: 18 months
Secondary outcomes:
measure: Composite Cardiovascular (CV) Mortality and Cardiovascular (CV) Hospitalization
timeFrame: 18 months
measure: New York Heart Association (NYHA) Class
timeFrame: 18 months
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: 18 months
measure: Cardiovascular (CV) Mortality
timeFrame: 18 months
measure: Cardiovascular (CV) Hospitalization
timeFrame: 18 months
measure: All-cause Mortality
timeFrame: 18 months
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Clinical Trial Site
state: California
city: Beverly Hills
country: United States
facility: Clinical Trial Site
state: California
city: La Mesa
country: United States
facility: Clinical Trial Site
state: California
city: Los Angeles
country: United States
facility: Clinical Trial Site
state: California
city: San Francisco
country: United States
facility: Clinical Trial Site
state: California
city: Stanford
country: United States
facility: Clinical Trial Site
state: California
city: Torrance
country: United States
facility: Clinical Trial Site
state: California
city: Aurora
country: United States
facility: Clinical Trial Site
state: Colorado
city: Washington
country: United States
facility: Clinical Trial Site
state: District of Columbia
city: Washington
country: United States
facility: Clinical Trial Site
state: District of Columbia
city: Tampa
country: United States
facility: Clinical Trial Site
state: Florida
city: Atlanta
country: United States
facility: Clinical Trial Site
state: Georgia
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: New Orleans
country: United States
facility: Clinical Trial Site
state: Louisiana
city: Baltimore
country: United States
facility: Clinical Trial Site
state: Maryland
city: Baltimore
country: United States
facility: Clinical Trial Site
state: Maryland
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Detroit
country: United States
facility: Clinical Trial Site
state: Michigan
city: Rochester
country: United States
facility: Clinical Trial Site
state: Minnesota
city: Saint Louis
country: United States
facility: Clinical Trial Site
state: Missouri
city: Newark
country: United States
facility: Clinical Trial Site
state: New Jersey
city: Bronx
country: United States
facility: Clinical Trial Site
state: New York
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Rosedale
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: Cleveland
country: United States
facility: Clinical Trial Site
state: Ohio
city: Columbus
country: United States
facility: Clinical Trial Site
state: Ohio
city: Philadelphia
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Charleston
country: United States
facility: Clinical Trial Site
state: South Carolina
city: Nashville
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Dallas
country: United States
facility: Clinical Trial Site
state: Texas
city: Fort Worth
country: United States
facility: Clinical Trial Site
state: Texas
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: Richmond
country: United States
facility: Clinical Trial Site
state: Virginia
city: Seattle
country: United States
facility: Clinical Trial Site
state: Washington
city: Anderlecht
country: Belgium
facility: Clinical Trial Site
city: Hasselt
country: Belgium
facility: Clinical Trial Site
city: Roeselare
country: Belgium
facility: Clinical Trial Site
city: Toronto
country: Canada
facility: Clinical Trial Site
city: Bordeaux
country: France
facility: Clinical Trial Site
state: Aquitaine
city: Creteil
country: France
facility: Clinical Trial Site
city: Marseille
country: France
facility: Clinical Trial Site
city: Paris
country: France
facility: Clinical Trial Site
city: Heidelberg
country: Germany
facility: Clinical Trial Site
city: Muenster
country: Germany
facility: Clinical Trial Site
city: Bologna
country: Italy
facility: Clinical Trial Site
city: Messina
country: Italy
facility: Clinical Trial Site
city: Pavia
country: Italy
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Umea
country: Sweden
facility: Clinical Trial Site
city: Croydon
country: United Kingdom
facility: Clinical Trial Site
state: England
city: London
country: United Kingdom
facility: Clinical Trial Site
state: England
city: Tooting
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Jared Gollob, MD
role: STUDY_DIRECTOR
References:
citation: Judge DP, Kristen AV, Grogan M, Maurer MS, Falk RH, Hanna M, Gillmore J, Garg P, Vaishnaw AK, Harrop J, Powell C, Karsten V, Zhang X, Sweetser MT, Vest J, Hawkins PN. Phase 3 Multicenter Study of Revusiran in Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis with Cardiomyopathy (ENDEAVOUR). Cardiovasc Drugs Ther. 2020 Jun;34(3):357-370. doi: 10.1007/s10557-019-06919-4.