ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)

Amyloidosis, Hereditary Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02319005
• Other study ID #: ALN-TTRSC-004
• Status: Completed
• Phase: Phase 3
• Start date: December 2014
• Est. completion date: March 30, 2017

Study information

• Verified date: June 2018
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: March 30, 2017
• Est. primary completion date: March 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyloid Neuropathies
• Amyloid Neuropathies, Familial
• Amyloidosis
• Amyloidosis, Familial
• Amyloidosis, Hereditary
• Amyloidosis, Hereditary, Transthyretin-Related
• Cardiomyopathies
• Familial Transthyretin Cardiac Amyloidosis
• Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)

Intervention

Drug:
• Revusiran (ALN-TTRSC)

• Sterile Normal Saline (0.9% NaCl)

Locations

Country	Name	City	State
Belgium	Clinical Trial Site	Anderlecht
Belgium	Clinical Trial Site	Hasselt
Belgium	Clinical Trial Site	Roeselare
Canada	Clinical Trial Site	Toronto
France	Clinical Trial Site	Bordeaux	Aquitaine
France	Clinical Trial Site	Creteil
France	Clinical Trial Site	Marseille
France	Clinical Trial Site	Paris
Germany	Clinical Trial Site	Heidelberg
Germany	Clinical Trial Site	Muenster
Italy	Clinical Trial Site	Bologna
Italy	Clinical Trial Site	Messina
Italy	Clinical Trial Site	Pavia
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Madrid
Sweden	Clinical Trial Site	Umea
United Kingdom	Clinical Trial Site	Croydon	England
United Kingdom	Clinical Trial Site	London	England
United Kingdom	Clinical Trial Site	Tooting
United States	Clinical Trial Site	Atlanta	Georgia
United States	Clinical Trial Site	Aurora	Colorado
United States	Clinical Trial Site	Bakersfield	California
United States	Clinical Trial Site	Baltimore	Maryland
United States	Clinical Trial Site	Baltimore	Maryland
United States	Clinical Trial Site	Beverly Hills	California
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Bronx	New York
United States	Clinical Trial Site	Charleston	South Carolina
United States	Clinical Trial Site	Chicago	Illinois
United States	Clinical Trial Site	Chicago	Illinois
United States	Clinical Trial Site	Chicago	Illinois
United States	Clinical Trial Site	Cleveland	Ohio
United States	Clinical Trial Site	Cleveland	Ohio
United States	Clinical Trial Site	Columbus	Ohio
United States	Clinical Trial Site	Dallas	Texas
United States	Clinical Trial Site	Detroit	Michigan
United States	Clinical Trial Site	Durham	North Carolina
United States	Clinical Trial Site	Fort Worth	Texas
United States	Clinical Trial Site	Houston	Texas
United States	Clinical Trial Site	La Mesa	California
United States	Clinical Trial Site	Los Angeles	California
United States	Clinical Trial Site	Nashville	Tennessee
United States	Clinical Trial Site	New Orleans	Louisiana
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Newark	New Jersey
United States	Clinical Trial Site	Philadelphia	Pennsylvania
United States	Clinical Trial Site	Philadelphia	Pennsylvania
United States	Clinical Trial Site	Richmond	Virginia
United States	Clinical Trial Site	Rochester	Minnesota
United States	Clinical Trial Site	Rosedale	New York
United States	Clinical Trial Site	Saint Louis	Missouri
United States	Clinical Trial Site	San Francisco	California
United States	Clinical Trial Site	Seattle	Washington
United States	Clinical Trial Site	Stanford	California
United States	Clinical Trial Site	Tampa	Florida
United States	Clinical Trial Site	Torrance	California
United States	Clinical Trial Site	Washington	District of Columbia
United States	Clinical Trial Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6 Minute Walk Distance (6-MWD)	The difference between revusiran and placebo group in change from baseline to 18 months in the total distance walked in 6 minutes	18 months
Primary	Serum TTR Levels	The difference between revusiran (ALN-TTRSC) and placebo group in the percent reduction in serum TTR levels over 18 months	18 months
Secondary	Composite Cardiovascular (CV) Mortality and Cardiovascular (CV) Hospitalization	Number of cardiovascular-related deaths and cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group	18 months
Secondary	New York Heart Association (NYHA) Class	The difference between revusiran (ALN-TTRSC) and placebo group in the change from baseline to 18 months in the NYHA class	18 months
Secondary	Kansas City Cardiomyopathy Questionnaire (KCCQ)	The difference between revusiran (ALN-TTRSC) and placebo group in the change from Baseline to 18 months in the Kansas City Cardiomyopathy Questionnaire	18 months
Secondary	Cardiovascular (CV) Mortality	Number of cardiovascular-related deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group	18 months
Secondary	Cardiovascular (CV) Hospitalization	Number of cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group	18 months
Secondary	All-cause Mortality	Total number of deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group	18 months