Inclusion Criteria:

• Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
• Be male or female ≥ 18 to ≤ 90 years of age.
• Have an established diagnosis of ATTR-CM with either wild-type TTR or a variant TTR genotype confirmed by genotyping, based on either:
  • endomyocardial biopsy with mass spectrometric analysis or immunoelectron microscopy; or
  • positive technetium-99m (99mTc)-pyrophosphate or -bisphosphonate scan, combined with accepted laboratory criteria excluding a diagnosis of AL amyloidosis (based on both immunofixation electrophoresis (IFE) of serum and urine, and serum free light chain (sFLC) analysis). Subjects with concurrent monoclonal gammopathy of undetermined significance (MGUS) may require confirmation of the diagnosis of ATTR-CM by endomyocardial biopsy with mass spectrometric analysis or immunoelectron microscopy.
• 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 (e.g., elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, or peripheral edema); or
  • heart failure symptoms that required or require ongoing treatment with a diuretic.
• Have NYHA Class I-III symptoms due to ATTR cardiomyopathy.
• Female subjects of childbearing potential who engage in heterosexual intercourse must agree to use highly effective methods of contraception beginning with randomization and continuing for 30 days after the last dose of AG10. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control.
• For subjects taking cardiovascular medical therapy, with the exception of diuretic dosing, must be on stable doses (defined as no greater than 50% dose adjustment and no categorical changes of medications) for at least 2 weeks prior to Screening.
• Have completed ≥ 150 m on the 6MWT on 2 tests prior to randomization.
• Must have NT-proBNP levels ≥300 pg/mL at Screening.
• Must have LV wall (interventricular septum or LV posterior wall) thickness ≥ 12 mm as measured by transthoracic echocardiogram (ECHO) or cardiac magnetic resonance (CMR) documented in medical history within 10 years of Screening or at Screening ECHO or CMR.

 Exclusion Criteria: 

• Acute myocardial infarction, acute coronary syndrome or coronary revascularization within 90 days prior to Screening.
• Stroke or TIA within 90 days prior to Screening.
• Has hemodynamic instability at Screening or Randomization that, in the judgment of the Investigator, would pose too great a risk for participation in the study.
• Is likely to undergo heart transplantation within a year of Screening.
• Has confirmed diagnosis of light-chain amyloidosis.
• Has abnormal liver function tests at Screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN) or total bilirubin > 3 × ULN.
• Has NT-proBNP levels ≥ 8500 pg/mL at Screening.
• Has estimated glomerular filtration rate (eGFR) by MDRD formula < 15 mL/min/1.73 m^2 at Screening.
• Known hypersensitivity to study drug (AG10 or placebo), its metabolites, or formulation excipients.
• Treatment for ATTR-CM with tafamidis, with marketed drug products lacking a labeled indication for ATTR-CM (e.g., diflunisal, doxycycline), or with natural products or derivatives used as unproven therapies for ATTR-CM (e.g., green tea extract, tauroursodeoxycholic acid [TUDCA]/ursodiol) within 14 days prior to dosing; treatment with patisiran, inotersen, or other gene silencing agent: within 90 days for patisiran, 180 days for inotersen, and 5 half-lives for any other gene silencing agent, prior to dosing. If, during participation in the study, subjects gain access to tafamidis, they will be permitted to initiate therapy with tafamidis as a concomitant medication if they have completed at least 24 months of blinded study therapy.
• Requires 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.
• Females who are pregnant or breastfeeding. Lactating females must agree to discontinue nursing before study drug is administered. A negative urine pregnancy test at Screening and at Randomization are required for female subjects of childbearing potential.
• In the judgment of the Investigator or Medical Monitor, has any clinically important ongoing medical condition or laboratory abnormality or condition that might jeopardize the subject’s safety, increase their risk from participation, or interfere with the study.
• Participation in another investigational drug or investigational device study within 30 days prior to dosing with potential residual effects that might confound the results of this study.
• Has any condition that, in the opinion of the Investigator or Medical Monitor, would preclude compliance with the study protocol such as a history of substance abuse, alcoholism or a psychiatric condition.