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

Primary Purpose

Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC), Amyloidosis, Hereditary, Amyloid Neuropathies, Familial

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Revusiran (ALN-TTRSC)
Sterile Normal Saline (0.9% NaCl)
Sponsored by
Alnylam Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC) focused on measuring Cardiomyopathy, Heart Failure, FAC, Amyloid, Transthyretin, TTR, RNAi therapeutic

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Revusiran (ALN-TTRSC)

Sterile Normal Saline (0.9% NaCl)

Arm Description

administered by subcutaneous (SC) injection

administered by subcutaneous (SC) injection

Outcomes

Primary Outcome Measures

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
Serum TTR Levels
The difference between revusiran (ALN-TTRSC) and placebo group in the percent reduction in serum TTR levels over 18 months

Secondary Outcome Measures

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
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
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
Cardiovascular (CV) Mortality
Number of cardiovascular-related deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Cardiovascular (CV) Hospitalization
Number of cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
All-cause Mortality
Total number of deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group

Full Information

First Posted
December 12, 2014
Last Updated
June 22, 2018
Sponsor
Alnylam Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02319005
Brief Title
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

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
March 30, 2017 (Actual)
Study Completion Date
March 30, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alnylam Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
206 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Revusiran (ALN-TTRSC)
Arm Type
Active Comparator
Arm Description
administered by subcutaneous (SC) injection
Arm Title
Sterile Normal Saline (0.9% NaCl)
Arm Type
Placebo Comparator
Arm Description
administered by subcutaneous (SC) injection
Intervention Type
Drug
Intervention Name(s)
Revusiran (ALN-TTRSC)
Intervention Type
Drug
Intervention Name(s)
Sterile Normal Saline (0.9% NaCl)
Primary Outcome Measure Information:
Title
6 Minute Walk Distance (6-MWD)
Description
The difference between revusiran and placebo group in change from baseline to 18 months in the total distance walked in 6 minutes
Time Frame
18 months
Title
Serum TTR Levels
Description
The difference between revusiran (ALN-TTRSC) and placebo group in the percent reduction in serum TTR levels over 18 months
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Composite Cardiovascular (CV) Mortality and Cardiovascular (CV) Hospitalization
Description
Number of cardiovascular-related deaths and cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Time Frame
18 months
Title
New York Heart Association (NYHA) Class
Description
The difference between revusiran (ALN-TTRSC) and placebo group in the change from baseline to 18 months in the NYHA class
Time Frame
18 months
Title
Kansas City Cardiomyopathy Questionnaire (KCCQ)
Description
The difference between revusiran (ALN-TTRSC) and placebo group in the change from Baseline to 18 months in the Kansas City Cardiomyopathy Questionnaire
Time Frame
18 months
Title
Cardiovascular (CV) Mortality
Description
Number of cardiovascular-related deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Time Frame
18 months
Title
Cardiovascular (CV) Hospitalization
Description
Number of cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Time Frame
18 months
Title
All-cause Mortality
Description
Total number of deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jared Gollob, MD
Organizational Affiliation
Alnylam Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Trial Site
City
Bakersfield
State/Province
California
Country
United States
Facility Name
Clinical Trial Site
City
Beverly Hills
State/Province
California
Country
United States
Facility Name
Clinical Trial Site
City
La Mesa
State/Province
California
Country
United States
Facility Name
Clinical Trial Site
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Clinical Trial Site
City
San Francisco
State/Province
California
Country
United States
Facility Name
Clinical Trial Site
City
Stanford
State/Province
California
Country
United States
Facility Name
Clinical Trial Site
City
Torrance
State/Province
California
Country
United States
Facility Name
Clinical Trial Site
City
Aurora
State/Province
Colorado
Country
United States
Facility Name
Clinical Trial Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
Clinical Trial Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20422
Country
United States
Facility Name
Clinical Trial Site
City
Tampa
State/Province
Florida
Country
United States
Facility Name
Clinical Trial Site
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Clinical Trial Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Clinical Trial Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Clinical Trial Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Clinical Trial Site
City
New Orleans
State/Province
Louisiana
Country
United States
Facility Name
Clinical Trial Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Clinical Trial Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Clinical Trial Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Clinical Trial Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Clinical Trial Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
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Detroit
State/Province
Michigan
Country
United States
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Rochester
State/Province
Minnesota
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United States
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Saint Louis
State/Province
Missouri
Country
United States
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Newark
State/Province
New Jersey
Country
United States
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City
Bronx
State/Province
New York
Country
United States
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City
New York
State/Province
New York
Country
United States
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City
Rosedale
State/Province
New York
Country
United States
Facility Name
Clinical Trial Site
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
Clinical Trial Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Clinical Trial Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Clinical Trial Site
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
Clinical Trial Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19102
Country
United States
Facility Name
Clinical Trial Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Clinical Trial Site
City
Charleston
State/Province
South Carolina
Country
United States
Facility Name
Clinical Trial Site
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Clinical Trial Site
City
Dallas
State/Province
Texas
Country
United States
Facility Name
Clinical Trial Site
City
Fort Worth
State/Province
Texas
Country
United States
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Clinical Trial Site
City
Houston
State/Province
Texas
Country
United States
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Richmond
State/Province
Virginia
Country
United States
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Seattle
State/Province
Washington
Country
United States
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Anderlecht
Country
Belgium
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City
Hasselt
Country
Belgium
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Roeselare
Country
Belgium
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Toronto
Country
Canada
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City
Bordeaux
State/Province
Aquitaine
Country
France
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Clinical Trial Site
City
Creteil
Country
France
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Clinical Trial Site
City
Marseille
Country
France
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City
Paris
Country
France
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Clinical Trial Site
City
Heidelberg
Country
Germany
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Muenster
Country
Germany
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Bologna
Country
Italy
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City
Messina
Country
Italy
Facility Name
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City
Pavia
Country
Italy
Facility Name
Clinical Trial Site
City
Barcelona
ZIP/Postal Code
8003
Country
Spain
Facility Name
Clinical Trial Site
City
Barcelona
ZIP/Postal Code
8907
Country
Spain
Facility Name
Clinical Trial Site
City
Madrid
Country
Spain
Facility Name
Clinical Trial Site
City
Umea
Country
Sweden
Facility Name
Clinical Trial Site
City
Croydon
State/Province
England
Country
United Kingdom
Facility Name
Clinical Trial Site
City
London
State/Province
England
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Tooting
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
32062791
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. Erratum In: Cardiovasc Drugs Ther. 2020 Jun 16;:
Results Reference
derived

Learn more about this trial

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

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