Study of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein (FRSW107) as Prophylactic Treatment.

A Single-Arm, Open-Label, Multicenter Phase III Clinical Study Evaluating the Efficacy, Safety, Immunogenicity and Pharmacokinetics of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein (FRSW107) as Prophylactic Therapy in Patients With Severe Hemophilia A (Adults and Adolescents)

The indication for this product is to control and prophylaxis in patients with Hemophilia A (congenital Factor VIII deficiency):

The Primary Objective： To evaluate the efficacy of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) for prophylactic treatment in previously treated patients with severe Hemophilia A.

Secondary Objectives： To evaluate the health-related quality of life, pharmacokinetic (PK) profiles, safety and immunogenicity of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) for prophylactic treatment in previously treated subjects with severe Hemophilia A.

Inclusion Criteria:

1.12≤ age ≤65 year-old men; 2.Subjects with clinically confirmed severe hemophilia A, i.e. at screening (central laboratory testing) or previous medical records confirm: FⅧ activity < 1%; 3.Previous documented treatment with any recombinant and/or blood-derived coagulation factor Ⅷ products or cryoprecipitation products and dosed ≥150 exposure days (EDs≥150) ; 4.Normal prothrombin time (PT) or International Normalized Ratio (INR)<1.3; 5.Bleeding events were recorded in detail for at least 6 months prior to screening; 6.Fully understand and know about this study and sign informed consent to participate in the clinical study voluntarily, subject and/or their guardian can cooperate with them for bleeding treatment at home, and have the ability to complete all study procedures

Exclusion Criteria:

1. Known or suspected allergy to the investigational drug or its excipients, including mouse or hamster proteins;
2. Hypersensitivity or anaphylaxis after FⅧ or IgG2 injection in the past;
3. FⅧ inhibitor positive (≥0.6 BU/mL) during the screening period, or have a history of FⅧ inhibitor positive in the past, or a family history of FⅧ inhibitor positive;
4. Von Willebrand factor (vWF) antigen test results were lower than the lower limit of normal value;
5. Severe anemia at the screening stage (hemoglobin < 60 g/L);
6. Platelet count during screening period < 100×109 /L;
7. Abnormal liver function: Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) >3 times upper limit of normal (ULN); or Serum total bilirubin (TBIL) >1.5x ULN;
8. Subjects with abnormal renal function: Creatinine clearance (Ccr) <50 ml/min (according to Cockcroft and Gault formula); or Serum creatinine (Cr) >1.5x ULN;
9. Subjects with active hepatitis C, that is, hepatitis C virus (HCV) antibody positive and HCV RNA positive; Or anti-treponema pallidum specific antibody (TPHA) positive; Or positive for antibodies against the human immunodeficiency virus (HIV);
10. Subjects with coagulation dysfunction other than hemophilia A;
11. Have a medical condition that may increase the risk of bleeding;
12. A history of drug or alcohol abuse;
13. Have a known mental disorder that may affect trial compliance;
14. Subjects who have received transfusions of blood or blood components within 4 weeks prior to screening;
15. Participants who had participated in other Interventional clinical trials within 1 month before screening;
16. Use of any anticoagulant or antiplatelet drugs, off-label maximum dose of non-steroidal anti-inflammatory drugs (NSAID) within 7 days prior to screening; Or subjects who need to be treated with anticoagulant or antiplatelet drugs or off-label maximum doses of SAID during clinical trials;
17. Severe cardiovascular and cerebrovascular disease or major thromboembolic events, such as stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association [NYHA] grade ≥ III), and severe arrhythmias (including QTc interphase > 480 ms, corrected by Fridericia formula), uncontrolled hypertension (systolic ≥ 160 mmHg or diastolic ≥100 mmHg), deep vein thrombosis, etc.
18. Subjects who have received emicizumab within 6 months prior to the first administration of study drug, or have previously received fitusiran (siRNA, brand name: CEPHEIN®) or gene therapy;
19. Subjects who have received monoclonal antibody therapy, Fc fusion protein products, or intravenous immunoglobulin within 3 months prior to the first administration of study drug;
20. Subjects who have undergone major surgery within 3 months prior to the first administration of study drug, or those who plan to receive surgery during the study period;
21. Subjects who have received any standard half-life FⅧ preparations (e.g., Advate, Kovaltry, Octate, Recombinate, NovoEight, Anjiyin, etc.) within 3 days or 5 half-lives (whichever is longer) prior to the first administration of study drug; patients who have received any other extended half-life FⅧ preparations (e.g., Noxyte) within 4 days or 5 half-lives (whichever is longer) prior to the first administration of study drug;
22. Study patients with fever, severe active bacterial or viral infection, and allergies within 2 weeks before the first administration of the drug;
23. Systemic immunomodulators (such as glucocorticoids [> 10 mg/ day equivalent dose of prednisone], alpha-interferon, immunoglobulin, cyclophosphamide, cyclosporin, etc.) used within 14 days prior to the first administration of the study drug or planned during the study period were allowed to be inhaled, nasal spray, or topical corticosteroids;
24. Those who had been vaccinated within 4 weeks prior to initial administration of the study drug; Or who plan to be vaccinated during PK blood collection (only for subjects in the PK subgroup);
25. Plan to have a child or sperm donation during the entire trial period and within 3 months after the last dose, or do not want to use effective physical contraception (such as condoms, diaphragms, Iuds, etc.);
26. Have other serious medical conditions that the researchers said could not benefit from them
27. Subjects deemed unsuitable by other investigators.