A Study to Evaluate Patisiran in Participants with Transthyretin Amyloidosis with Cardiomyopathy (ATTR Amyloidosis with Cardiomyopathy)


About this study

The purpose of this study is to evaluate the effectiveness and safety of patisiran in participants with Transthyretin Amyloidosis With Cardiomyopathy.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria: 

  • Age 18 (or age of legal consent, whichever is older) to 85 years, inclusive.
  • Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hereditary ATTR amyloidosis with cardiomyopathy or wild-type ATTR amyloidosis with cardiomyopathy:
    • Hereditary ATTR amyloidosis with cardiomyopathy diagnosed based on meeting all of the following criteria:
      • TTR pathogenic mutation consistent with hATTR;
      • 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 (eg, 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] or 99mTc-pyrophosphate [PYP-Tc]) with Grade 2 or 3 cardiac uptake, if monoclonal gammopathy of undetermined significance (MGUS) has been excluded;
      • If MGUS, confirm TTR protein in tissue with immunohistochemistry (IHC) or mass spectrometry.
    • Wild-type ATTR amyloidosis with cardiomyopathy diagnosed based on meeting all of the following criteria:
      • 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 precursor identification by IHC, mass spectrometry, OR technetium (99mTc) scintigraphy (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid [DPD-Tc] or 99mTc-pyrophosphate [PYP-Tc]) with Grade 2 or 3 cardiac uptake, if MGUS has been excluded;
      • If MGUS, confirm TTR protein in cardiac tissue with IHC or mass spectrometry.
  • Medical history of heart failure with at least 1 prior hospitalization for heart failure, or current clinical evidence (signs and symptoms of heart failure).
  • Clinically stable with no cardiovascular related hospitalizations within 6 weeks of study start.
  • Has never taken tafamidis before (tafamidis naïve) or currently on tafamidis for ≥ 6 months with evidence of disease progression while on tafamidis treatment.
  • Able to complete ≥ 150 m on the 6-minute walk test.
  • Screening N-terminal pro B-type natriuretic peptide (NT-proBNP), a blood marker of heart failure severity, > 300 ng/L and < 8500 ng/L.
  • Patient is able to understand and is willing and able to comply with the study requirements and to provide written informed consent; and patient agrees to sign the medical records release form for collection of vital status.

Exclusion Criteria: 

  • Has known primary amyloidosis (AL) or leptomeningeal amyloidosis.
  • NYHA Class III AND ATTR amyloidosis disease Stage 3 (defined as both NT-proBNP >3000 ng/L and estimated glomerular filtration rate [eGFR] <45 ml/min/1.73 m^2).[Gillmore 2018]
  • NYHA Class IV at the Screening visit.
  • Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV (requires cane or stick to walk, or is wheelchair bound) at the Screening visit.
  • Has any of the following laboratory parameter assessments at screening:
    • Aspartate transaminase (AST) or alanine transaminase (ALT) levels ˃2.0 × the upper limit of normal (ULN);
    • Total bilirubin ˃ULN. Patients with elevated total bilirubin that is secondary to documented Gilbert’s syndrome are eligible if total bilirubin <2 × ULN
    • International normalized ratio (INR) ˃1.5 (unless patient is 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).
  • Has known human immunodeficiency virus infection; or evidence of current or chronic hepatitis C virus or hepatitis B virus infection.
  • Tafamidis naïve patients (at baseline) for whom the Investigator actively plans or anticipates commencing treatment with tafamidis during the 12-month double-blind period, taking into consideration clinical status, patient preference and/or commercial availability of tafamidis.
  • Is currently taking diflunisal; if previously on this agent, must have at least a 6-month wash-out prior to dosing (Day 1).
  • Is currently taking doxycycline, or tauroursodeoxycholic acid; if previously on any of these agents, must have completed a 30-day wash-out prior to dosing (Day 1).
  • Received prior TTR-lowering treatment or participated in a gene therapy trial for hATTR amyloidosis.
  • 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 6 months prior to dosing (Day 1) is required; this does not apply to patients who are on tafamidis at baseline.
  • Requires treatment with calcium channel blockers (e.g., verapamil, diltiazem) or digitalis.
  • 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 electrocardiogram [ECG] changes).
  • Has non-amyloid disease affecting exercise testing (e.g., severe chronic obstructive pulmonary disease, severe arthritis, or peripheral vascular disease affecting ambulation).
  • Recent or planned orthopedic procedure during the double-blind period (e.g., lower extremity or back surgery) that could impact 6-MWT.
  • Unstable congestive heart failure (CHF) (eg, no adjustment of diuretics at time of screening required to achieve optimal treatment 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 (˃180 mmHg) and diastolic (˃100 mmHg) blood pressure that is considered uncontrolled by physician.
  • Has untreated hypo- or hyperthyroidism.
  • Prior or planned heart, liver, or other organ transplant.
  • Had a malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
  • Has other medical conditions or comorbidities 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 or breast-feeding.
  • Has a known history of alcohol abuse within the past 2 years or daily heavy alcohol consumption (for females, more than 14 units of alcohol per week; for males, more than 21 units of alcohol per week [unit: 1 glass of wine [125 mL] = 1 measure of spirits = ½ pint of beer]);
  • 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.


Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Martha Grogan, M.D.

Closed for enrollment

Contact information:

Susanna Miller R.N., CCRP

(507) 538-5468


More information


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