Phase 3 N=632 Randomized Quadruple-blind Treatment

Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy

Amyloidosis · Amyloid Cardiomyopathy · Transthyretin Amyloidosis · Cardiomyopathies · Heart Diseases

Bottom Line

View on ClinicalTrials.gov: NCT03860935 ↗

Enrolled (actual)

632

Serious AEs

58.1%

Results posted

Jun 2024

Primary outcome: Primary: A Hierarchical Combination of All-Cause Mortality, Cumulative Frequency of CV-related Hospitalization, Change From Baseline in NT-proBNP and Change From Baseline in 6MWT at the Last Available Visit Where Both Subjects Had Non-missing Assessments. — 63.7; 35.9 Percent of Wins from Win Ratio — p=<0.0001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: acoramidis (Drug); Placebo Oral Tablet (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Eidos Therapeutics, a BridgeBio company
Primary completion: May 2023

Outcome Measures

Outcome	Result	p-value
PRIMARY A Hierarchical Combination of All-Cause Mortality, Cumulative Frequency of CV-related Hospitalization, Change From Baseline in NT-proBNP and Change From Baseline in 6MWT at the Last Available Visit Where Both Subjects Had Non-missing Assessments.	63.7; 35.9	<0.0001 sig
SECONDARY Change From Baseline to Month 30 in the Distance Walked During the 6 Minute Walk Test (6MWT)	-64.65; -104.29	<0.0001 sig
SECONDARY Change From Baseline to Month 30 of the Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS)	-11.48; -21.42	<0.0001 sig
SECONDARY Change From Baseline to Month 30 in Serum TTR (Prealbumin) Level	5.78; -1.32	<0.0001 sig
SECONDARY All-cause Mortality by Month 30, Including Death Due to Any Cause, Heart Transplant or Cardiac Mechanical Assist Device (CMAD)	79; 52	0.0569

Summary

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).

Eligibility Criteria

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03860935). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.