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.
Brief Title
ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)
Amyloidosis, Hereditary
Amyloid Neuropathies, Familial
Amyloid Neuropathies
Amyloidosis, Hereditary, Transthyretin-Related
Familial Transthyretin Cardiac Amyloidosis
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
* 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
Inclusion 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
* Documented TTR mutation
* Amyloid deposits in cardiac or non-cardiac tissue
* Medical history of heart failure
* Evidence of cardiac involvement by echocardiogram
Gender
All
Gender Based
false
Keywords
Cardiomyopathy
Heart Failure
FAC
Amyloid
Transthyretin
TTR
RNAi therapeutic
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
90 Years
Minimum Age
18 Years
NCT Id
NCT02319005
Org Class
Industry
Org Full Name
Alnylam Pharmaceuticals
Org Study Id
ALN-TTRSC-004
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome Description
The difference between revusiran and placebo group in change from baseline to 18 months in the total distance walked in 6 minutes
Outcome Measure
6 Minute Walk Distance (6-MWD)
Outcome Time Frame
18 months
Outcome Description
The difference between revusiran (ALN-TTRSC) and placebo group in the percent reduction in serum TTR levels over 18 months
Outcome Measure
Serum TTR Levels
Outcome Time Frame
18 months
Secondary Outcomes
Outcome Description
Number of cardiovascular-related deaths and cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Outcome Time Frame
18 months
Outcome Measure
Composite Cardiovascular (CV) Mortality and Cardiovascular (CV) Hospitalization
Outcome Description
The difference between revusiran (ALN-TTRSC) and placebo group in the change from baseline to 18 months in the NYHA class
Outcome Time Frame
18 months
Outcome Measure
New York Heart Association (NYHA) Class
Outcome Description
The difference between revusiran (ALN-TTRSC) and placebo group in the change from Baseline to 18 months in the Kansas City Cardiomyopathy Questionnaire
Outcome Time Frame
18 months
Outcome Measure
Kansas City Cardiomyopathy Questionnaire (KCCQ)
Outcome Description
Number of cardiovascular-related deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Outcome Time Frame
18 months
Outcome Measure
Cardiovascular (CV) Mortality
Outcome Description
Number of cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Outcome Time Frame
18 months
Outcome Measure
Cardiovascular (CV) Hospitalization
Outcome Description
Total number of deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group
Outcome Time Frame
18 months
Outcome Measure
All-cause Mortality
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
90
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
James Tauras
Investigator Email
jtauras@montefiore.org
Investigator Phone
Categories Mesh Debug
Heart/Cardiovascular --- HEART FAILURE
Diabetes --- METABOLIC DISEASES
Diabetes & Endocrine System --- METABOLIC DISEASES
Brain, Spinal Cord & Nervous System --- NERVOUS SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- NERVOUS SYSTEM DISEASES
Brain, Spinal Cord & Nervous System --- PERIPHERAL NERVOUS SYSTEM DISEASES
Brain, Spinal Cord & Nervous System --- NEUROMUSCULAR DISEASES
Brain, Spinal Cord & Nervous System --- HEART DISEASES
Heart/Cardiovascular --- HEART DISEASES
Blood Disorders --- CARDIOVASCULAR DISEASES
Blood & Bone Marrow Cancers --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- CARDIOVASCULAR DISEASES
Alzheimer's --- DEMENTIA
Alzheimer's --- BRAIN DISEASES
Brain, Spinal Cord & Nervous System --- BRAIN DISEASES
Brain, Spine & Nerve Cancers --- BRAIN DISEASES
Alzheimer's --- CENTRAL NERVOUS SYSTEM DISEASES
Brain, Spinal Cord & Nervous System --- CENTRAL NERVOUS SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- CENTRAL NERVOUS SYSTEM DISEASES
Alzheimer's --- NEUROCOGNITIVE DISORDERS
Child Development & Autism --- MENTAL DISORDERS
Mental Health & Behavioral Research --- MENTAL DISORDERS
Psychiatry & Behavioral Sciences --- MENTAL DISORDERS
Substance Use and Addiction --- MENTAL DISORDERS
MeSH Terms
AMYLOIDOSIS, FAMILIAL
AMYLOID NEUROPATHIES, FAMILIAL
AMYLOID NEUROPATHIES
AMYLOIDOSIS, HEREDITARY, TRANSTHYRETIN-RELATED
CARDIOMYOPATHIES
HEART FAILURE
ALZHEIMER DISEASE
METABOLISM, INBORN ERRORS
GENETIC DISEASES, INBORN
CONGENITAL, HEREDITARY, AND NEONATAL DISEASES AND ABNORMALITIES
METABOLIC DISEASES
NUTRITIONAL AND METABOLIC DISEASES
AMYLOIDOSIS
PROTEOSTASIS DEFICIENCIES
HEREDODEGENERATIVE DISORDERS, NERVOUS SYSTEM
NEURODEGENERATIVE DISEASES
NERVOUS SYSTEM DISEASES
PERIPHERAL NERVOUS SYSTEM DISEASES
NEUROMUSCULAR DISEASES
HEART DISEASES
CARDIOVASCULAR DISEASES
DEMENTIA
BRAIN DISEASES
CENTRAL NERVOUS SYSTEM DISEASES
TAUOPATHIES
NEUROCOGNITIVE DISORDERS
MENTAL DISORDERS
REVUSIRAN