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

Phase 3

Completed

• Conditions: Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC); Amyloid Neuropathies, Familial; Amyloidosis, Hereditary, Transthyretin-Related; Amyloid Neuropathies; Familial Transthyretin Cardiac Amyloidosis; Amyloidosis, Hereditary
• Interventions: Drug: Revusiran (ALN-TTRSC); Drug: Sterile Normal Saline (0.9% NaCl)

• Registration Number: NCT02319005
• Lead Sponsor: Alnylam Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-12
• Study First Submitted: 2014-12-12
• Study First Submitted QC: 2014-12-17
• Study First Posted: 2014-12-18
• Primary Completion: 2017-03-30
• Study Completion: 2017-03-30
• Results First Submitted: 2018-03-27
• Status Verified: 2018-06
• Results First Submitted QC: 2018-06-22
• Last Update Submitted: 2018-06-22
• Results First Posted: 2018-07-18
• Last Update Posted: 2018-07-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 206

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Revusiran (ALN-TTRSC)	Revusiran (ALN-TTRSC)	administered by subcutaneous (SC) injection
Sterile Normal Saline (0.9% NaCl)	Sterile Normal Saline (0.9% NaCl)	administered by subcutaneous (SC) injection

Primary Outcome Measures

Name	Time	Method
6 Minute Walk Distance (6-MWD)	18 months	The difference between revusiran and placebo group in change from baseline to 18 months in the total distance walked in 6 minutes
Serum TTR Levels	18 months	The difference between revusiran (ALN-TTRSC) and placebo group in the percent reduction in serum TTR levels over 18 months

Secondary Outcome Measures

Name	Time	Method
Composite Cardiovascular (CV) Mortality and Cardiovascular (CV) Hospitalization	18 months	Number of cardiovascular-related deaths and cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
New York Heart Association (NYHA) Class	18 months	The difference between revusiran (ALN-TTRSC) and placebo group in the change from baseline to 18 months in the NYHA class
Cardiovascular (CV) Mortality	18 months	Number of cardiovascular-related deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
All-cause Mortality	18 months	Total number of deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Kansas City Cardiomyopathy Questionnaire (KCCQ)	18 months	The difference between revusiran (ALN-TTRSC) and placebo group in the change from Baseline to 18 months in the Kansas City Cardiomyopathy Questionnaire
Cardiovascular (CV) Hospitalization	18 months	Number of cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group

Trial Locations

Locations (1)

Clinical Trial Site; 🇬🇧 Tooting, United Kingdom