Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Controlled, Parallel, Prospective Trial to Evaluate the Effect of Secondary Prophylaxis With rFVIII Therapy in Severe Hemophilia A Adult and/or Adolescent Subjects, as Applicable, Compared to That of Episodic Treatment
Brief Summary: To evaluate the effect of secondary prophylaxis as compared to episodic treatment on bleeding frequency (number of bleeds per year) and on joint damage.


Options:
A: Inclusion Criteria:

* Male patients with moderately severe or severe congenital haemophilia B with a factor IX activity of 2% or below according to medical records
* History of at least 150 exposure days to other factor IX products
* Patients currently treated on-demand with at least 6 bleeding episodes during the last 12 months or at least 3 bleeding episodes during the last 6 months, or patients currently on prophylaxis

Exclusion Criteria:

* Known history of factor IX inhibitors based on existing medical records, laboratory report reviews and patient and legally acceptable representative (LAR) interviews
* HIV (Human immunodeficiency virus) positive, with a viral load equal to or above 400,000 copies/mL and/or CD4+ lymphocyte count equal to or below 200/microL
* Congenital or acquired coagulation disorders other than haemophilia B
* Previous arterial thrombotic events (e.g. myocardial infarction and intracranial thrombosis) or previous deep venous thrombosis or pulmonary embolism (as defined by available medical records)
* Immune modulating or chemotherapeutic medication
B: Inclusion Criteria:

* Males aged 12 to 50 years (US and Argentina)
* Males aged 18 to 50 years (other countries)
* Subjects with severe hemophilia A (\<1% FVIII:C) as confirmed by the central lab from a sample obtained at least 96 hours after FVIII administration wash-out. Allow for the inclusion of a maximum of 10% (n=8) of patients with 1-2% FVIII:C baseline levels as long as they exhibit clinical severity and comply with all other inclusion criteria.
* Subjects with at least 150 prior exposure days with any FVIII
* Subjects who have been on episodic treatment and no known regular prophylaxis treatment for more than 12 consecutive months in the previous 5 years
* Subjects with 6 to 24 bleeding events and/or treatments in the previous 6 months prior to study entry which are documented and available in the subjects medical records. Documentation can include records from previous physicians, specific home treatment records, emergency room or hospital records, x-ray reports, etc. The investigator can also document with a detailed note the number of bleeds reported by the subject in the last 6 months.
* Subjects with inhibitor formation surveillance (inhibitor or recovery testing) over the ten years prior to enrollment documented by the investigator and who do not have a history of any of the following:

  * A positive inhibitor titer of 5.0 Bethesda Unit (BU) or greater by either BU assay system at any time since first exposure to exogenous factor VIII
  * A positive inhibitor test result of 1.0 or greater performed by the original BU assay at any time in the past 10 years (A subject can have more than one positive inhibitor test of 0.6 or greater by the original BU assay test but all must be less than 1.0 BU using the original BU assay.)
  * A positive inhibitor test result of 0.6 or greater performed by the Nijmegen method at any time in the past 10 years
* Subjects with no inhibitor activity by Nijmegen-modified Bethesda assay, either positive (\> 0.6 BU is considered positive) or borderline (\> 0.3 and \< 0.6 BU is considered borderline) as measured in the current study reference laboratory

Exclusion Criteria:

* Subjects with any other bleeding disease besides hemophilia A (i.e. von Willebrand disease)
* Subjects with thrombocytopenia (platelets \< 100,000/mm3)
* Subjects with abnormal renal function (Cockcroft-Gault Creatinine Clearance value of 60 mL/min or lower)
* Subjects with active hepatic disease (Aspartate aminotransferase \[AST\] or Alanine aminotransferase \[ALT\] \> 5xUpper Limit of Normal (ULN))
* Subjects on treatment with immunomodulatory agents within the last 3 months prior to study entry or during the study (the following drugs are however allowed: interferon-a treatment for Hepatitis C virus (HCV), Highly active anti-retroviral therapy (HAART) therapy for human immunodeficiency virus (HIV) and/or a total of two courses of pulse treatment with steroids for a maximum of 7 days at 1mg/kg or less)
* Subjects with an absolute CD4 lymphocyte cell count \< 200 cells/mm3 (due to HIV, HCV or another suspected medical condition)
* Subjects with known hypersensitivity to rFVIII, mouse or hamster proteins
* Subjects who are receiving or had received other experimental drugs within 1 month prior to study entry
* Subjects who require any pre-medication to tolerate FVIII injections (e.g. anti-histamines)
* Subjects who are unwilling to comply with study visits or either of the possible treatment regimens
* Subjects who have a planned orthopedic intervention to be performed during the study that may substantially affect bleeding (e.g. surgical or chemical or radiological synovectomy)
* Subjects who are not suitable for participation in this study for any reason, according to the Investigator
* Subjects who have poor joint status as defined by routine need for a wheelchair or unable to ambulate without the assistance of a brace, cane or crutches
* Three or more joints that are already fused or "frozen" also called ankylosis
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:

* Participants with severe hemophilia A (baseline FVIII activity FVIII:C \<1%), determined by measurement at the time of screening (following a washout period of at least 72 h after their last FVIII treatment for standard half-life FVIII products or of 120 h for extended half-life FVIII products) or from reliable prior documentation (e.g. measurement in other clinical studies, result from approved clinical laboratory or diagnostic genetic testing).
* ≥150 exposure days with FVIII concentrate(s) (plasma-derived or recombinant) as supported by medical records.
* Body mass index (BMI) within the range 18 kg/m2 to 29.9 kg/m2 (inclusive).

Exclusion Criteria:

* Inability to stop FVIII treatment to complete a minimum of 72 h washout for standard half-life FVIII product or 120 h washout for extended half-life FVIII product
* Evidence of current or past inhibitor antibody
* History of any congenital or acquired coagulation disorders other than hemophilia A
* Platelet count \<75,000/mm3
* Human immunodeficiency virus (HIV) infection with a cluster of differentiation 4 (CD4+) lymphocyte count of \<200/mm3
* Abnormal renal function (serum creatinine \>2x the upper limit of the normal range \[ULN\])
* Active liver disease verified by medical history or persistently elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>5x ULN or severe liver disease as evidenced by, but not limited to any of the following: International Normalized Ratio \>1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices
* Requirement of any pre-medication to tolerate FVIII treatment (e.g. anti-histamines)
* Prior treatment with immunomodulatory agents or chemotherapy within the last 3 months prior to study entry or requirement of treatment during the study. The following drugs are allowed: α interferon, PEG interferon, highly active anti-retroviral therapy for HIV, and/or a total of two courses of pulse treatment with steroid for a maximum of 7 days at 1 mg/kg or less

Answer: B