Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy

Purpose

Phase 3 efficacy and safety study to evaluate acoramidis (AG10) HCl 800 mg administered orally twice a day 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 that are within 15% of total distance walked prior to randomization - Biomarkers of myocardial wall stress, NT-proBNP level ≥300 pg/mL at screening - 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

ArmDescriptionAssigned Intervention
Experimental
acoramidis HCl 800 mg
Subjects will receive acoramidis HCl 800 mg twice daily. 6MWT primary outcome will be assessed at the end of 12 months. The hierarchical combination of All-Cause mortality, cumulative frequency of cardiovascular-related hospitalizations, change from baseline in NT-proBNP levels, and change from baseline in distance walked on the 6MWT will be assessed after 30 months of treatment.
  • Drug: acoramidis
    TTR stabilizer administered orally twice daily (BID)
    Other names:
    • AG10
    • ALXN2060
Placebo Comparator
Placebo
Subjects will receive placebo to match twice daily. 6MWT primary outcome will be assessed at the end of 12 months. The hierarchical combination of All-Cause mortality, cumulative frequency of cardiovascular-related hospitalizations, change from baseline in NT-proBNP levels, and change from baseline in distance walked on the 6MWT will be assessed after 30 months of treatment.
  • Drug: Placebo Oral Tablet
    Non-active control administered orally twice daily (BID)

More Details

Status
Completed
Sponsor
Eidos Therapeutics, a BridgeBio company

Study Contact

Detailed Description

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed condition believed to affect more than 400,000 people worldwide. In ATTR-CM, the accumulation of transthyretin (TTR) amyloid results in thickening and stiffening of the heart, which often leads to heart failure or even death. There are two forms of ATTR-CM: - Wild Type* This form of the condition primarily develops in older individuals who do not carry gene mutations. - Hereditary* This form of the condition comes from gene mutations passed down in families. In this study we are researching the investigational drug acoramidis HCl 800 mg administered orally twice a day. Through the study, we want to evaluate the efficacy and safety of acoramidis in patients with ATTR-CM versus placebo. This is a 30 month, randomized, double-blind, placebo-controlled study. This means that, during the 30 month study, investigators conducting the research and study participants will not know whether the study participant is receiving acoramidis or placebo. The primary outcomes of the study are: 1. The impact of acoramidis versus placebo on the change in distance walked on the 6 minute walk test (6MWT) after 12 months of treatment compared to baseline. 2. The impact of acoramidis versus placebo on the hierarchical combination of All-Cause mortality, cumulative frequency of cardiovascular-related hospitalizations, change from baseline in NT-proBNP, and change in from baseline in 6MWT over a 30-month fixed treatment duration. At the end of 30 months, participants may be eligible to receive investigational acoramidis, and there is no placebo. This is called an "open label extension." This separate study may help us better understand the safety related to taking acoramidis over a longer period of time.