Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2, Open-Label, Multi-Dose, Dose Escalation Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous Infusions of ALN-TTR02 in Patients With TTR Amyloidosis
Brief Summary: This was a multiple dose, dose escalation study designed to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of patisiran (ALN-TTR02) in participants with transthyretin (TTR) mediated amyloidosis (ATTR).


Options:
A: Key Inclusion criteria:

* Subject had successfully completed either Protocol Fx-006 or Fx-1A-201.
* Male or female subjects with ATTR-PN who had not undergone liver or heart transplantation at time of enrollment.
* If female, subject was post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control

Key Exclusion criteria:

* Chronic use of non-protocol approved non-steroidal anti-inflammatory drugs (NSAIDs)
* Pregnant or breast feeding female subjects.
* Clinically significant medical condition that, in the opinion of the investigator, would place the subject at an increased risk to participate in the study.
* An alanine aminotransferase (ALT) and aspartate aminotransferase (AST) value \>3 × upper limit of normal (ULN) that, in the medical judgment of the investigator, was due to reduced liver function or active liver disease.
* Sexually active males with partners of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 3 months after last dose of study drug.
B: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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 enrollment.
* 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 \< 30 ml/min).
* 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 disease.
* 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).
C: Inclusion Criteria:

* Male or female of 18 to 85 years of age (inclusive);
* Have a diagnosis of FAP
* Neuropathy Impairment Score requirement of 5-130
* Meet Karnofsky performance status requirements
* Have adequate complete blood counts and liver function tests
* Have adequate cardiac function
* Have negative serology for hepatitis B virus (HBV) and hepatitis C virus (HCV)

Exclusion Criteria:

* Had a prior liver transplant or is planned to undergo liver transplant during the study period;
* Has untreated hypo- or hyperthyroidism;
* Has known human immunodeficiency virus (HIV) infection;
* Had a malignancy within 2 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated;
* Recently received an investigational agent or device
* Is currently taking diflunisal, tafamidis, doxycycline, or tauroursodeoxycholic acid
D: Inclusion Criteria:

* Body mass index must be between 17 kg/m\^2 and ≤ 33 kg/m\^2;
* Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must use appropriate contraception;
* Males agree to use appropriate contraception;
* Diagnosis of TTR amyloidosis;
* Adequate blood counts, liver and renal function;
* Willing to give written informed consent and are willing to comply with the study requirements.

Exclusion Criteria:

* Known human immunodeficiency virus (HIV) positive status or known or suspected systemic bacterial, viral, parasitic, or fungal infection;
* Received an investigational agent, other than tafamidis or diflunisal, within 30 days prior to first dose study drug administration;
* Prior liver transplant;
* Poor cardiac function;
* Considered unfit for the study by the Principal Investigator;
* Employee or family member of the sponsor or the clinical study site personnel.

Answer: D