Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
Purpose
Phase 3 efficacy and safety study to evaluate AG10 800 mg compared to placebo in subjects with symptomatic Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
Conditions
- Amyloidosis
- Amyloid Cardiomyopathy
- Transthyretin Amyloidosis
- Cardiomyopathies
- Heart Diseases
Eligibility
- Eligible Ages
- Between 18 Years and 90 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Have an established diagnosis of ATTR-CM with either wild-type TTR or variant TTR genotype
- Have a history of heart failure evidenced by at least one prior hospitalization for heart failure or clinical evidence of heart failure without prior heart failure hospitalization manifested by signs or symptoms of volume overload or elevated intracardiac pressures or heart failure symptoms that required or require ongoing treatment with a diuretic.
- New York Heart Association (NYHA) Class I-III symptoms due to ATTR cardiomyopathy.
- On stable doses of cardiovascular medical therapy
- Completed ≥150 m on the 6MWT on 2 tests prior to randomization
- Biomarkers of myocardial wall stress, NT-proBNP level ≥300 pg/mL
- Have left ventricular wall (interventricular septum or left ventricular posterior wall) thickness ≥12 mm
Exclusion Criteria
- Had acute myocardial infarction, acute coronary syndrome or coronary revascularization, or experienced stroke or transient ischemic attack within 90 days prior to screening
- Has hemodynamic instability
- Likely to undergo heart transplantation within a year of screening
- Confirmed diagnosis of primary (light chain) amyloidosis
- Biomarkers of myocardial wall stress, NT-proBNP level ≥8500 pg/mL at screening
- Measure of kidney function, eGFR by MDRD formula <15 mL/min/1.73 m2
- Current treatment with marketed drug products and other investigational agents for the treatment of ATTR-CM
- Current treatment with calcium channel blockers with conduction system effects (e.g. verapamil, diltiazem). The use of dihydropyridine calcium channel blockers is allowed. The use of digitalis will only be allowed if required for management of atrial fibrillation with rapid ventricular response
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental AG10 800 mg |
Subjects will receive AG10 800 mg twice daily. 6 Minute Walk Test (6MWT) primary outcome will be assessed at the end of 12 months, followed by all-cause mortality and cardiovascular-related hospitalization assessed at the end of 30 months. |
|
|
Placebo Comparator Placebo |
Subjects will receive placebo to match twice daily. 6 Minute Walk Test (6MWT) primary outcome will be assessed at the end of 12 months, followed by all-cause mortality and cardiovascular-related hospitalization assessed at the end of 30 months. |
|
Recruiting Locations
Washington, District of Columbia 20010
More Details
- NCT ID
- NCT03860935
- Status
- Recruiting
- Sponsor
- Eidos Therapeutics
Detailed Description
This Phase 3 prospective, randomized, multicenter, parallel-group study will evaluate the efficacy and safety of AG10 800 mg in subjects with symptomatic Transthyretin Amyloid Cardiomyopathy (ATTR-CM) for a total of 30 months of blinded, placebo-controlled treatment.
At the end of 12 months of treatment (Part A) efficacy of AG10 will be assessed through analyses of the functional endpoint, 6 Minute Walk Test, and the health-related Quality of Life endpoint, heart failure-specific instrument Kansas City Cardiomyopathy Questionnaire.
At the end of 30 months of treatment (Part B) efficacy of AG10 will be further assessed through analysis of all-cause mortality and frequency of cardiovascular-related hospitalization.
All subjects who complete 30 months of blinded, placebo-controlled treatment may be eligible to participate in an open label extension study of long-term AG10 treatment.