Please select the eligibility criteria that correspond to the clinical trial below.
Title: B-LONG: An Open-Label, Multicenter Evaluation of the Safety, Pharmacokinetics, and Efficacy of Recombinant, Long-acting Coagulation Factor IX Fc Fusion Protein (rFIXFc) in the Prevention and Treatment of Bleeding in Previously Treated Subjects With Severe Hemophilia B
Brief Summary: The primary objectives of the study were: to evaluate the safety and tolerability of rFIXFc; to evaluate the efficacy of rFIXFc in all treatment arms; to evaluate the effectiveness of prophylaxis over on-demand (episodic) therapy by comparing the annualized number of bleeding episodes between participants receiving rFIXFc on each prevention (prophylaxis) regimen and participants receiving rFIXFc on an episodic regimen. The secondary objectives of the study were: to evaluate and assess the pharmacokinetic (PK) parameter estimates of rFIXFc and rFIX (BeneFIX®) at baseline in the Sequential PK subgroup as well as rFIXFc at Week 26 (±1 week); to evaluate participants' response to treatment; to evaluate rFIXFc consumption.


Options:
A: Main Inclusion Criteria:

* Participant and/or legal representative has/have voluntarily provided signed informed consent
* Participant is 12 to 65 years old at the time of screening
* Participant is male with severe hemophilia A (Factor VIII (FVIII) clotting activity \< 1%) as confirmed by central laboratory at screening after the appropriate washout period or a documented FVIII clotting activity \<1%
* Participant has been previously treated with plasma-derived FVIII concentrates or recombinant FVIII for ≥150 documented exposure days (EDs)
* Participant is currently receiving prophylaxis or on-demand therapy with FVIII
* Participant is willing and able to comply with the requirements of the protocol

Main Exclusion Criteria:

* Participant has detectable FVIII inhibitory antibodies (≥ 0.6 Bethesda Units (BU) using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening
* Participant has history of FVIII inhibitory antibodies (≥ 0.4 BU using the Nijmegen modification of the Bethesda assay or ≥ 0.6 BU using the Bethesda assay) at any time prior to screening
* Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).
B: Inclusion Criteria:

* Male and 12 years of age and older and weigh at least 40 kg
* Diagnosed with hemophilia B (baseline Factor IX level less than or equal to 2%)
* History of at least 100 exposure days to any Factor IX product
* Platelet count ≥100,000 cells/μL

Exclusion Criteria:

* History of Factor IX inhibitors
* Kidney or liver dysfunction
* Diagnosed with another coagulation defect other than hemophilia B
* Prior history of anaphylaxis associated with any Factor IX or intravenous (IV) immunoglobulin administration
C: Inclusion Criteria:

* Males ≥ 18 years of age with established severe HB (FIX:C\<1u/dl),
* Treated/exposed to FIX products (e.g., concentrates or fresh frozen plasma) for at least 10 years or 50 exposure days.
* A minimum of an average of 3 bleeding episodes per year requiring FIX infusions or prophylactic FIX infusions because of frequent prior bleeding episodes
* Able to give informed consent and comply with requirements of the trial
* Currently free of inhibitor and have no history of inhibitors to FIX protein
* A negative family history for the development of an inhibitor,
* Willing to practice a reliable barrier method of contraception until 3 sequential samples are negative for vector genomes using our PCR assay.

Exclusion Criteria:

* Evidence of active infection with Hepatitis B or C virus as reflected by HBsAg or NCV RNA positivity, respectively. To be considered negative for active infection, two negative assays at a minimum of a six month interval are required.
* Exposure to Hepatitis B or C who are currently on antiviral therapy.
* Serological evidence of HTLV or active HIV infection. Individuals who are effectively being treated with antiretroviral therapy are eligible. Specific criteria for effectiveness of treatment include the following:

  * Documented CD4+ T-cell count of \> 350 cells/mm\^3.
  * HIV-1 RNA viral load \< 400 copy/ml for at least the past 12 months, including at least 2 viral load test results of \< 400 copy/ml during the immediate 12 month interval prior to screening.
  * Screening HIV-RNA viral load \< 400 copies/ml.
  * Stable HAART regimen (drugs of at least 2 different classes) for at least 12 months prior to study entry. Treatment regimen changes for dosing convenience and in response to toxicity are permitted.
  * Documented and confirmed (repeated) viral loads of ≥ 400 copies/ml during the 12 month time interval prior to screening are bases for exclusion although a single, unconfirmed, "glimpse" of ≥ 400 copies/ml are permitted.
* Significant liver dysfunction as defined by an abnormal ALT (alanine transaminase), bilirubin, alkaline phosphatase or INR. Potential participants who have had a liver biopsy in the past 3 years will be excluded if they have significant fibrosis of 3 or 4 as rated on a scale of 0-4.
* Coronary artery disease as a co-morbid condition
* Platelet count of \<50 x 10\^9/l
* Creatinine ≥ 1.5 mg/dl
* Hypertension with systolic blood pressure (BP) ≥ 140 mmHg or diastolic BP ≥ 90 mmHg
* History of active tuberculosis, fungal disease or other chronic infection
* History of chronic disease that would adversely affect performance other than hemophilic arthropathy
* Detectable antibodies reactive with AAV8
* Subjects who are unwilling to provide the required semen samples
* Poor performance status (WHO performance status score \>1) or
* Received an AAV vector or any other gene transfer agent in the previous 6 months
* Presence of lung nodule(s) suspicious of malignancy on screening chest tomography
* Presence of liver abnormalities suspicious of malignancy on screening liver ultrasound
D: Inclusion Criteria:

* Diagnosed with hemophilia A
* factor level less than 2%

Exclusion Criteria:

* More than 2 bleeds into the same joint

Answer: B