Please select the eligibility criteria that correspond to the clinical trial below.
Title: Single Dose, Open Label, Randomized, Cross-over Study in Participants With Severe Hemophilia A Comparing Pharmacokinetic Parameters of BAY 94-9027 and Adynovi
Brief Summary: This study is being conducted to compare how the body distributes and excretes the drugs Jivi (BAY 94-9027) and Adynovi. Jivi is a recently approved blood clotting Factor VIII (FVIII) medication for the treatment of hemophilia A (bleeding disorder resulting from a lack of FVIII). Both drugs are FVIII products which have been manufactured via recombinant technology and have an extended half-live, i.e. they will stay longer in the body than other FVIII products. Therefore these products act longer in the body which reduces the frequency of drug injections. To compare the two drugs, a cross-over design was chosen, i.e. each patient will receive both products one after another.

Patients participating in this study will receive one dose of Jivi and one dose of Adynovi. Both drugs are injected into a vein. Observation will last for about 10 weeks, and blood samples will be taken from the participants to measure the blood levels of FVIII. Generic name of Jivi is Damoctocog-alfa-pegol, generic name of Adynovi is Rurioctocog alfa pegol.


Options:
A: 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
B: Inclusion Criteria:

* Male subjects diagnosed with haemophilia A without inhibitors present at screening and currently treated on-demand
* Subjects with a baseline level of factor VIII below or equal to 2 % based on medical records
* Age between 18 and 64 years both inclusive, at the time of signing informed consent
* Body weight between 50 and 100 kg, both inclusive

Exclusion Criteria:

* Known or suspected hypersensitivity to trial product or related products
* Platelet count below 50x10\^9/L at screening
* Any clinical signs or known history of thromboembolic events, or subjects considered at high risk of thromboembolic events as judged by the investigator
* Subjects at increased risk of cardiovascular disease as judged by the investigator
C: Inclusion Criteria:

* age ≥ 12 years and ≤ 55 years
* severe haemophilia A (FVIII \< 1%)
* absence of inhibitors (Bethesda titre \< 0.6 BU/ml)
* Previous Treated Patients (prior exposure days \> 200)
* Kogenate Bayer administered 20-30 IU/kg -3 times a week, for the prophylaxis group
* ≥ 6 joint bleeds requiring treatment with FVIII concentrates in the previous 6 months before enrollment, for on-demand group
* written informed consent

Exclusion Criteria:

* concomitant severe and chronic diseases or congenital skeletal malformation
* unreliability of patient or likelihood of follow-up failure
* presence of inhibitors or history of inhibitors (in the previous 2 years)
* currently on immune tolerance treatment
* hepatic cirrhosis or liver disease in rapid progression
* AIDS
* platelet count \< 75,000/mm3
* presence of conditions that influence negatively patient´s compliance
* participation in another study
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: D