Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Open-Label Study To Compare On-Demand Treatment With 2 Prophylaxis Regimens of Recombinant Coagulation Factor IX (BeneFIX) Reformulated Drug Product (rFIX-R) In Subjects With Severe Hemophilia B
Brief Summary: This study is designed to evaluate BeneFIX infused as prophylaxis regimens, compared with BeneFIX administered as an on-demand regimen only. In the trial, subjects will participate in 4 study periods. The first period is a 16-week on-demand treatment, during which subjects will utilize BeneFIX to treat bleeding events episodically only as they occur (i.e., on-demand treatment). At the end of this period, subjects will be randomly assigned to 1 of 2 BeneFIX prophylaxis regimens: either 100 IU/kg once weekly or 50 IU/kg twice weekly, and followed for 16 weeks. At the end of this period, subjects will use on-demand treatment for 8 weeks. The purpose of this 8-week period is to mitigate the potential carry-over effect of the prior prophylaxis regimen on bleeding frequency. Following this 8-week on-demand treatment, subjects will cross-over and receive the alternate study prophylactic regimen for 16 weeks.

The primary endpoint is annualized number of bleeding episodes, compared between the first on-demand period and each of the prophylaxis regimens. A comparison of annualized bleeding episodes between the two prophylaxis regimens will also be performed. Subject-reported outcomes will also be collected using a patient diary. At 24 and 48 hours following the onset of each joint bleeding episode, information on pain, sleep, and work will be collected. Additional data on physical functioning will be recorded on the diary at the end of the 16-week on-demand period, and at the end of each prophylaxis period. Information on safety will also be collected.

Each subject will participate in this study for approximately 59 weeks (15 months), including a screening period of up to 3 weeks, an initial 16-week on-demand period, two prophylaxis treatment periods of 16 weeks each, separated by an 8-week on-demand treatment period.

A modified FIX recovery study will be performed once during each prophylaxis period.

The study diary will also be used by subjects to collect secondary endpoints. These endpoints, which are subject-reported outcomes, will be recorded in the diary at 24 and 48 hours following the onset of each joint bleeding episode. Additional data on physical functioning will be recorded on the diary at the end of the 16-week on-demand period, and at the end of each prophylaxis period.

Patients will be recruited in the United States, Canada, Europe and Russia.


Options:
A: Inclusion Criteria:

* Body weight \>/= 40 kilograms (kg) at the time of screening
* Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor ( that is \[i.e.\], \>/= 5 Bethesda Units \[BU\])
* Documentation of treatment with episodic or prophylactic bypassing agents for at least the last 24 weeks
* \>/= 6 bleeds in the last 24 weeks prior to screening (if on an episodic bypassing agent regimen) or \>/=2 bleeds in the last 24 weeks prior to screening (if on a prophylactic bypassing agent regimen)
* Adequate hematologic, hepatic and renal function
* For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use single or combined highly effective contraceptive methods

Exclusion Criteria:

* Participants with inherited or acquired bleeding disorder other than hemophilia A
* Participants with ongoing (or plan to receive during the study) immune tolerance induction therapy or prophylaxis with Factor VIII (FVIII), with the exception of participants who have received a treatment regimen of FVIII prophylaxis with concurrent bypassing agent prophylaxis
* Previous (in the past 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which antithrombotic treatment is not currently ongoing) or current signs of thromboembolic disease
* Participants with other conditions (for example \[e.g.\], certain autoimmune diseases) that may increase the risk of bleeding or thrombosis
* History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
* Known human immunodeficiency virus (HIV) infection with cluster of differentiation 4 (CD4) count \< 200 cells per microliter (cells/mcL) within 24 weeks prior to screening
* Use of systemic immunomodulators (e.g., interferon or rituximab) at enrolment or planned use during the study, with the exception of antiretroviral therapy
* Participants who are at high risk for thrombotic microangiopathy (TMA; e.g., have a previous medical or family history of TMA), in the investigator's judgment
* Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the investigator or Sponsor, preclude the participant's safe participation in and completion of the study or interpretation of the study results
* Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study
* Receipt of emicizumab in a prior investigational study; An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration; A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter; An investigational drug concurrently
* Unwillingness to use highly effective contraception methods for the specified duration in the protocol (females only, unless required otherwise by the local health authority)
* Clinically significant abnormality on screening evaluations or laboratory tests that, in the opinion of the investigator, may pose an additional risk in administering study drug to the participant
* Pregnancy or lactation, or intent to become pregnant during the study
B: Key Inclusion Criteria:

* Subjects who have completed previous rFVIIIFc studies (NCT01181128, NCT02083965, NCT01458106 and NCT02502149)
* Ability to understand purposes and risks of the study and to provide signed and dated informed consent (or assent, as applicable).

Key Exclusion Criteria:

* Confirmed positive high-titer inhibitor (≥5.00 BU/mL).

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
C: Inclusion Criteria:

* Male, aged 18-70 years (both inclusive) at the time of signing informed consent
* Patients with the diagnosis of congenital haemophilia B with factor IX activity below or equal to 2%, based on medical records
* History of more than 150 exposures days to any factor IX containing products

Exclusion Criteria:

* Known history of factor IX inhibitors
* Inhibitors to factor IX (above or equal to 0.6 BU) at screening measured by the Nijmegen modified Bethesda method
* Immunocompromised (CD4+ T cells below or equal to 200/μL)
* Known congenital or acquired coagulation disorders other than haemophilia B
* Body mass index above 35 kg/m\^²
D: Inclusion Criteria:

* Documented history of moderately severe or severe hemophilia B (FIX:C less than or equal to 2%)
* Male subjects, aged 6 years to 65 years.
* Subjects with a minimum of 12 bleeding episodes, 6 of which must be joint bleeds, in the 12 months before screening.

Exclusion Criteria:

* Subjects currently utilizing FIX primary prophylaxis.
* Subjects with HIV+ who have a CD4 count less than 200
* Subjects with hepatic or renal impairment.
* Prothrombin time or International Normalized Ration more than 1.5 times the upper limit of normal.
* Major surgery or an orthopedic surgical procedure within the past 3 months or is planned within the duration of participation in this study.
* Past history of, or current FIX inhibitor.
* Hypersensitivity to any FIX product or hamster protein.
* Exposure to any investigational drug, except for rFIX-R, or device within 30 days of providing consent/assent (as appropriate) for this study.
* Bleeding disorders other than hemophilia B.
* Concurrent inflammatory disease that in the investigator's judgment could confound the study results.

Answer: D