Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2/3, Multi-Center, Open Label Study of Efficacy, Safety, and Pharmacokinetics of PEGylated Recombinant Factor VIII (BAX 855) Administered for Prophylaxis and Treatment of Bleeding in Previously Treated Patients With Severe Hemophilia A
Brief Summary: To assess efficacy and safety, including immunogenicity of BAX 855 administered as prophylaxis and as on-demand therapy in adult and adolescent (12-65 years) previously treated patients (PTPs) with severe hemophilia A To determine the pharmacokinetic (PK) parameters of BAX 855.


Options:
A: 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
B: 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).
C: Inclusion Criteria:

* Male subjects, 12 to 65 years old
* Severe hemophilia B (FIX activity of ≤ 2%)
* Subjects who have received FIX products (plasma-derived and/or recombinant FIX) for \> 150 exposure days (EDs)
* No history of FIX inhibitor formation, no detectable inhibitors at Screening and no family history of inhibitors against FIX
* Written informed consent for study participation
* On-demand subjects only, who have experienced a minimum average of 2 non-trauma induced bleeding episodes requiring treatment with a FIX product during the previous 6 or 3 months

Exclusion Criteria:

* Known hypersensitivity to any FIX product or hamster protein
* Known congenital or acquired coagulation disorder other than congenital FIX deficiency
* HIV positive subjects with a CD4 count \< 200/mm3
* Low platelet count, kidney or liver dysfunction
* Recent life-threatening bleeding episode
D: 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

Answer: B