To evaluate the efficacy and safety of patisiran in patients with wtATTR amyloidosis and symptomatic polyneuropathy by evaluating the effect on neurologic impairment and quality of life.

The study will consist of a baseline screening period and a 24-month treatment period. Eligible patient will receive patisiran administered as an IV infusion once every 21 days for a 24-month period. During the 24-month treatment period study patients will undergo assessments for efficacy and/or safety as outlined in the schedule of assessments with key efficacy assessments being performed prior to the first dose and proceeding as outlined in the schedule of assessments.

Inclusion Criteria:

1. Male or female >18
2. Diagnosis of symptomatic polyneuropathy
3. wtATTR based on cardiac biopsy or Tc99m PYP
4. Negative hATTR sequencing
5. 0 to 0.5 gram/dl serum monoclonal protein.
6. No history of other secondary causes of neuropathy.
7. Have adequate complete blood counts and liver function tests
8. Have negative serology for hepatitis B virus (HBV) and hepatitis C virus (HCV)

Exclusion Criteria:

1. Other Causes of neuropathy as determined by the principle investigator.

2. Has known human immunodeficiency virus (HIV) infection;

3. Primary AL.

4. NYHA Class IV at the Screening visit. 5. Has any of the following laboratory parameter assessments at screening:

   1. Aspartate transaminase (AST) or alanine transaminase (ALT) levels ˃2.0 × the upper limit of normal (ULN).

   2. Total bilirubin ˃ULN. Patients with elevated total bilirubin that is secondary to documented Gilbert's syndrome are eligible if total bilirubin <2 × ULN.

   3. International normalized ratio (INR) ˃1.5 (unless patient is on anticoagulant therapy, in which case excluded if INR ˃3.5).

      6. Has eGFR < 30 mL/min/1.73 m2 (using the modification of diet in renal disease [MDRD] formula). 7. Is currently taking diflunisal; if previously on this agent, must have at least a 6-month wash-out prior to dosing (Day 1).

      8. 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).

      9. Received prior TTR-lowering treatment or participated in a gene therapy trial for amyloidosis. 10. 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 (per inclusion Criterion 4).

      11. Requires treatment with calcium channel blockers (eg, verapamil, diltiazem) or digitalis.

      12. Other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathy due to valvular heart disease, or cardiomyopathy due to ischemic heart disease.

      13. Has non-amyloid disease affecting exercise testing (eg, severe chronic obstructive pulmonary disease, severe arthritis, or peripheral vascular disease affecting ambulation).

      14. Had acute coronary syndrome or unstable angina within the past 3 months. 15. Has history of sustained ventricular tachycardia or aborted ventricular fibrillation.

      16. Has persistent elevation of systolic (˃180 mmHg) and diastolic (˃100 mmHg) blood pressure that is considered uncontrolled by physician.

17-Has untreated hypo- or hyperthyroidism. 18-Prior or planned heart, liver, or other organ transplant. 19. 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.

20. Has other medical conditions or comorbidities which, in the opinion of the Investigator would interfere with study compliance or data interpretation. 21. Female Is not willing to comply with the contraceptive requirements during the study period.

22. 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.

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