Active, not recruiting
Phase 3
Study of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein (FRSW107) as Prophylactic Treatment.
Condition(s) studied
Severe Hemophilia A
Investigational drug(s) / intervention(s)
FRSW107: For subjects in the PK subgroup: they will receive a dose of 50 IU/kg at the first dose visit 1 to obtain preliminary pharmacokinetic (PK) data. After assessment by the investigator, individualized prophylactic treatment (25\~50 IU/kg, Q3D) will be administered to maintain the trough concentration of FVIII activity at ≥1%.
For subjects not in the PK subgroup: they will receive prophylactic treatment at a dose of 25\~50 IU/kg once every three days.
If a subject experiences a breakthrough bleeding episode requiring treatment, the investigator shall determine the appropriate dosage (recommended dose range: 20\~50 IU/kg) and administration frequency.
Study summary
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.
Eligibility
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.
Primary outcome measure(s)
- ABR — 6 months
Annual rate of bleeding (ABR) during preventive treatment = Number of bleeding episode during the efficacy evaluation period/(number of treatment days /365.25)
Trial sites (19)
| Facility | City | Region | Status |
| Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College |
Tianjin |
Tianjin Municipality |
|
| Fuyang Hospital, Affiliated to Anhui Medical University |
Fuyang |
China |
|
| Fujian Medical University Union Hospital |
Fuzhou |
China |
|
| Nanfang Hospital of Southern Medical University |
Guangzhou |
China |
|
| Anhui Provincial Hospital |
Hefei |
China |
|
| Jinan central hospital |
Jinan |
China |
|
| The Second Affiliated Hospital of Kunming Medical University |
Kunming |
China |
|
| The First Affiliated Hospital of Guangxi Medical University |
Nanning |
China |
|
| Affiliated Hospital of Nantong University |
Nantong |
China |
|
| The First Affiliated Hospital of Nanyang Medical College |
Nanyang |
China |
|
| Qinghai Provincial People's Hospital |
Qinghai |
China |
|
| The Second Hospital of Shanxi Medical University |
Taiyuan |
China |
|
| North China University of Science and Technology Affiliated Hospital |
Tangshan |
China |
|
| Wenzhou People's Hospital |
Wenzhou |
China |
|
| Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology. |
Wuhan |
China |
|
| Affiliated Hospital of Jiangnan University |
Wuxi |
China |
|
| Xi'an Central Hospital |
Xi'an |
China |
|
| Henan Cancer Hospital |
Zhengzhou |
China |
|
| Zhengzhou People's Hospital |
Zhengzhou |
China |
|
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