Please select the eligibility criteria that correspond to the clinical trial below.
Title: APOLLO: A Phase 3 Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Patisiran (ALN-TTR02) in Transthyretin (TTR)-Mediated Polyneuropathy (Familial Amyloidotic Polyneuropathy-FAP)
Brief Summary: The purpose of this study is to evaluate the safety and efficacy of patisiran (ALN-TTR02) in patients with transthyretin (TTR) mediated amyloidosis. An open-label, single-arm, long-term follow-up extension study NCT02510261 (ALN-TTR02-006) was initiated to provide participants who completed this study with continued patisiran-LNP (lipid nanoparticle) treatment.


Options:
A: Inclusion Criteria:

1. Amyloid documented by biopsy.
2. Documented V30M TTR mutation.
3. Peripheral and/or autonomic neuropathy with a Karnofsky Performance Status ≥50.
4. Patient is 18-75 years old.
5. If female, patient is post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control. If male with a female partner of childbearing potential, willing to use an acceptable method of birth control for the duration of the study. For both females and males, birth control must be used for at least 3 months after the last dose of study medication.
6. 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:

1. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs).
2. Primary amyloidosis.
3. If female, patient is pregnant or breast feeding.
4. Prior liver transplantation.
5. No recordable sensory threshold for vibration perception in both feet, as measured by CASE IV.
6. Positive results for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV).
7. Renal insufficiency or liver function test abnormalities.
8. New York Heart Association (NYHA) Functional Classification ≥III.
9. Other causes of sensorimotor neuropathy (B12 deficiency, Diabetes Mellitus, HIV treated with retroviral medications, thyroid disorders, alcohol abuse, and chronic inflammatory diseases).
10. Co-morbidity anticipated to limit survival to less than 18 months.
11. Patient received an investigational drug/device and/or participated in another clinical investigational study within 60 days before Baseline.
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:

* 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).
D: 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

Answer: D