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

Study Overview
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Brief Summary
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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.

Official Title
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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)

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

Intervention / Treatment
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* Drug: Revusiran (ALN-TTRSC)
* Drug: Sterile Normal Saline (0.9% NaCl)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Revusiran (ALN-TTRSC)<br>administered by subcutaneous (SC) injection | Drug: Revusiran (ALN-TTRSC)<br> <br> |
| Placebo Comparator: Sterile Normal Saline (0.9% NaCl)<br>administered by subcutaneous (SC) injection | Drug: Sterile Normal Saline (0.9% NaCl)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| Cardiovascular (CV) Mortality | Number of cardiovascular-related deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group | 18 months | 
| Cardiovascular (CV) Hospitalization | Number of cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group | 18 months | 
| All-cause Mortality | Total number of deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiomyopathy, Heart Failure, FAC, Amyloid, Transthyretin, TTR, RNAi therapeutic