Inclusion Criteria:

• Age 18 (or age of legal consent per local regulations, whichever is older) to 85 years, inclusive.
• Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hATTR amyloidosis with cardiomyopathy or wtATTR amyloidosis with cardiomyopathy:
  • Hereditary ATTR (hATTR) amyloidosis with cardiomyopathy diagnosed based on meeting all of the following criteria:
  • Documentation of a TTR pathogenic mutation consistent with hATTR amyloidosis;
  • Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness > 12 mm (based on central echocardiogram reading at Screening);
  • Amyloid deposits in cardiac or noncardiac tissue (e.g., fat pad aspirate, salivary gland, median nerve connective sheath) confirmed by Congo Red (or equivalent) staining OR technetium (99mTc) scintigraphy (99mTc-3,3-diphosphono-1,2- propanodicarboxylic acid [DPD-Tc], 99mTc-pyrophosphate [PYP-Tc] or 99Tchydroxymethylene diphosphonate [HMDP]) with Grade 2 or 3 cardiac uptake, if monoclonal gammopathy of undetermined significance (MGUS) has been excluded;
  • If the patient has evidence of a MGUS based on serum and urine protein electrophoresis and serum free light chains,  documentation of TTR protein in tissue with immunohistochemistry or mass spectrometry is required.
  • Wild-type ATTR (wtATTR) amyloidosis with cardiomyopathy diagnosed based on meeting all of the following criteria:
    • Documentation of absence of pathogenic TTR mutation;
    • Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness > 12mm (based on central echocardiogram reading at Screening);
    • Amyloid deposits in cardiac tissue with TTR protein identification by IHC, mass spectrometry, OR technetium (99mTc) scintigraphy (99mTc-3,3-diphosphono-1,2- propanodicarboxylic acid [DPD-Tc], 99mTc-pyrophosphate [PYP-Tc], or 99Tchydroxymethylene diphosphonate [HMDP]) with Grade 2 or 3 cardiac uptake, if MGUS has been excluded;
    • If the patient has evidence of a MGUS based on serum and urine protein electrophoresis and serum free light chains, the following is required: documentation of TTR protein in cardiac tissue with immunohistochemistry or mass spectrometry OR documentation of TTR protein in noncardiac tissue (e.g., fat pad aspirate, salivary gland, median nerve connective sheath) with immunohistochemistry or mass spectrometry; AND Grade 2 or 3 cardiac uptake on technetium scintigraphy.
• Medical history of HF with at least 1 prior hospitalization for HF (not due to arrhythmia or a conduction system disturbance treated with a permanent pacemaker) OR clinical evidence of HF (with or without hospitalization) manifested by signs and 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, peripheral edema) that currently requires treatment with a diuretic.
• Patient meets one of the following criteria: a. Tafamidis-naïve and not actively planning to commence treatment with tafamidis during the first 12 months following randomization.
  • Note: in addition to patients who have never taken tafamidis, those who have previously been on tafamidis and have not received any tafamidis for at least 30 days before the Screening Visit will be considered tafamidis-naïve for purposes of this study); or
  • On tafamidis.  Note: must be on-label use of commercial tafamidis per an approved cardiomyopathy indication and dose in the country of use.
• Patient is clinically stable, with no CV-related hospitalizations within 6 weeks prior to randomization, as assessed by the Investigator.
• Screening NT-proBNP > 300 ng/L and 600 ng/L and < 8500 ng/L.
• Able to complete ≥ 150 meters on the 6-MWT at Screening.
• Have a Karnofsky performance status of ≥ 60%

Exclusion Criteria:

• Has known primary amyloidosis (AL amyloidosis) or leptomeningeal amyloidosis.
• NYHA Class IV heart failure; or NYHA Class III heart failure AND ATTR Amyloidosis Disease Stage 3 (defined as NT-proBNP > 3000 ng/L and eGFR < 45 ml/min).[Gillmore 2018].
• Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV (requires cane or stick to walk due to polyneuropathy, or is wheelchair bound) at the Screening visit.
• Has any of the following laboratory parameter assessments at Screening:
  • AST or ALT levels > 2.0 × ULN;
  • Total bilirubin > 2.0 × ULN;
  • International normalized ratio (INR) > 1.5 (unless patients were on anticoagulant therapy in which case excluded if INR ˃ 3.5).
• Has eGFR < 30 mL/min/1.73 m^2 (using the modification of diet in renal disease [MDRD] formula) at Screening.
• Has known human immunodeficiency virus infection; or evidence of current or chronic hepatitis C virus or hepatitis B virus infection.
• Tafamidis-naïve patients for whom the Investigator actively plans or anticipates commencing treatment with tafamidis either during the Screening Period or the first 12 months following randomization, taking into consideration clinical status, patient preference and/or commercial availability of tafamidis.
• Received prior TTR-lowering treatment (including revusiran, patisiran or inotersen) or participated in a gene therapy trial for hATTR amyloidosis.
• Is currently taking diflunisal; if previously on this agent, must have at least a 30-day wash-out prior to dosing (Day 1).
• Is currently taking doxycycline, ursodeoxycholic acid, or tauroursodeoxycholic acid; if previously on any of these agents, must have completed a 30-day wash-out prior to dosing (Day 1).
• Unwilling to avoid any concurrent treatment with diflunisal, ursodeoxycholic acid/tauroursodeoxycholate/doxycycline, or TTR lowering agents (e.g., patisiran, inotersen)
• Current or future participation in another investigational device or drug study, scheduled to occur during this study, or has received an investigational agent or device within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to dosing (Day 1). In the case of investigational TTR stabilizer drugs, washout for 3 months prior to dosing (Day 1) is required; this does not apply to patients who are on tafamidis at baseline.
• Requires treatment with or is unwilling to avoid any concurrent treatment with nondihydropyridine calcium channel blockers (e.g., verapamil, diltiazem).
• 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to dosing (Day 1). In the case of investigational TTR stabilizer drugs, washout for 3 months prior to dosing (Day 1) is required; this does not apply to patients who are on tafamidis at baseline.
• Requires treatment with or is unwilling to avoid any concurrent treatment with nondihydropyridine calcium channel blockers (e.g., verapamil, diltiazem).
• Other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathy due to valvular heart disease, or cardiomyopathy due to ischemic heart disease (e.g., prior myocardial infarction with documented history of cardiac enzymes and ECG changes) that the Investigator feels is a significant contributor or the predominant cause of the patient’s heart failure.
• Unstable congestive heart failure (CHF) (including patients who require adjustment of existing diuretics or addition of new diuretics at time of Screening for purposes of achieving optimal management of CHF).
• Had acute coronary syndrome or unstable angina within the past 3 months.
• Has history of sustained ventricular tachycardia or aborted ventricular fibrillation.
• Has history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker is indicated but will not be placed.
• Has persistent elevation of systolic (˃ 170 mmHg) or diastolic (˃ 100 mmHg) blood pressure that is considered uncontrolled by physician.
• Has untreated hypo- or hyperthyroidism.
• Has an active infection requiring systemic antiviral, antiparasitic or antimicrobial therapy that will not be completed prior to dosing (Day 1).
• Prior or anticipated (during the first 12 months after randomization) heart, liver or other organ transplant or implantation of left-ventricular assist device.
• History of multiple drug allergies or history of allergic reaction to any component of or excipient in the study drug.
• History of intolerance to SC injection(s) or significant abdominal scarring that could potentially hinder study drug administration or evaluation of local tolerability.
• Has other medical conditions or comorbidities (e.g., malignancy, neuropsychiatric disorder etc…) which, in the opinion of the Investigator, would interfere with study compliance or data interpretation.
• Is not willing to comply with the contraceptive requirements during the study period.
• Female patient is pregnant, planning a pregnancy, or breast-feeding.
• Unwilling or unable to limit alcohol consumption throughout the course of the study. Alcohol intake of > 2 units/day is excluded during the study (unit: 1 glass of wine [approximately 125 mL] = 1 measure of spirits [approximately 1 fluid ounce] = ½ pint of beer [approximately 284 mL]).
• History of alcohol abuse, within the last 12 months before Screening, in the opinion of the Investigator.
• History of illicit drug abuse within the past 5 years that in the opinion of the Investigator would interfere with compliance with study procedures or follow-up visits.