- Patient has amyloid documented by biopsy (in accordance with institutional site
standard of care).
- Patient has documentation of one of the following targeted TTR mutations: Ser77Tyr,
Thr60Ala, Tyr114Cys, Leu58His, Glu89Gln, Ser77Phe, Thr49Ala, Ile107Val, Val30Ala,
Gly47Ala, Gly47Glu, Leu55Arg, Lys70Asn, Ile84Thr, Ile107Met. Patients with mutations
other than those listed may be enrolled only after approval by the Sponsor.
- Patient has peripheral and/or autonomic neuropathy and/or cardiomyopathy with a
Karnofsky Performance Status ≥ 50.
- Patient is aged ≥18 to 75 years, inclusive.
- If female, patient is post-menopausal, surgically sterilized, or willing to use two
acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine
device, diaphragm with spermicide, condom with spermicide) throughout the study and
for 3 months from the end of the study. (A condom alone is not considered an
acceptable method of birth control.) If male with a female partner of childbearing
potential, willing to use two acceptable methods of birth control for the duration of
the study. For both females and males, acceptable birth control must be used for at
least 3 months after the last dose of study medication.
- Patient is, in the opinion of the investigator, willing and able to comply with the
study medication regimen and all other study requirements.
- Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), defined as greater than
3-4 times/month (ibuprofen and nimesulide will be permitted).
- Patient has primary or secondary amyloidosis.
- Patient has TTR-associated amyloidosis with V30M mutation.
- If female, patient is pregnant or breast feeding.
- Patient has received prior liver transplantation.
- Patient is expected to undergo liver transplantation within 12 months after
- Patient with positive results for hepatitis B surface antigen (HBsAg), anti-hepatitis
C virus (HCV), and/or human immunodeficiency virus (HIV).
- Patient has renal insufficiency (creatinine clearance
- Patient has liver function test abnormalities: alanine transaminases (ALT) and/or
aspartate transaminases (AST) > 2 times upper limit of normal (ULN) that in the
medical judgment of the investigator are due to reduced liver function or active liver
- Patient has a New York Heart Association (NYHA) Functional Classification ? III.
- Patient has other causes of sensorimotor neuropathy (B12 deficiency, Diabetes
Mellitus, HIV treated with retroviral medications, thyroid disorders, alcohol abuse,
and chronic inflammatory diseases).
- Patient has prior non-amyloid cardiac disease such as: myocardial infarction due to
obstructive coronary artery disease, active non-amyloid cardiomyopathy (e.g.,
symptomatic left ventricular dysfunction from any cause other than amyloid, patients
with a primary diagnosis of symptomatic valvular heart disease)
- Patient has a co-morbidity anticipated to limit survival to less than 12 months.
- Patient has received an investigational drug/device and/or participated in another
clinical investigational study within 60 days before Baseline (Day 0).