Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of ISIS 420915 in Patients With Familial Amyloid Polyneuropathy (NEURO-TTR Study)
Brief Summary: The purpose of this study is to evaluate the efficacy and safety of inotersen given for 65 weeks in participants with Familial Amyloid Polyneuropathy (FAP).


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:

* Medical history of Heart Failure (HF) with at least 1 prior hospitalization for HF or clinical evidence of HF (without hospitalization) manifested by signs or 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 required/requires treatment with a diuretic for improvement,
* Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness \> 12 mm,
* Presence of amyloid deposits in biopsy tissue and presence of a variant TTR genotype and/or TTR precursor protein identification by immunohistochemistry, scintigraphy or mass spectrometry

Exclusion Criteria:

* A New York Heart Association (NYHA) classification of IV.
* Presence of primary (light chain) amyloidosis.
* Prior liver or heart transplantation or implanted cardiac mechanical assist device.
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:

* Stage 1 and Stage 2 FAP participants with the following:

  1. NIS score within protocol criteria
  2. Documented transthyretin variant by genotyping
  3. Documented amyloid deposit by biopsy
* Females of child-bearing potential must use appropriate contraception and be non-pregnant and non-lactating. Males engaging in relations of child-bearing potential are to use appropriate contraception

Exclusion Criteria:

* Low Retinol level at screen
* Karnofsky performance status ≤50
* Poor Renal function
* Known type 1 or type 2 diabetes mellitus
* Other causes of sensorimotor or autonomic neuropathy (for example, autoimmune disease)
* If previously treated with Vyndaqel®, will need to have discontinued treatment for 2 weeks prior to Study Day 1. If previously treated with Diflunisal, will need to have discontinued treatment for 3 days prior to Study Day 1
* Previous treatment with any oligonucleotide or siRNA within 12 months of screening
* Prior liver transplant or anticipated liver transplant within 1 year of screening
* New York Heart Association (NYHA) functional classification of ≥3
* Acute Coronary Syndrome or major surgery within 3 months of screening
* Known Primary or Leptomeningeal Amyloidosis
* Anticipated survival less than 2 years
* Any other conditions in the opinion of the investigator which interfere with the participant participating in or completing the study

Answer: D