Active, not recruiting
Phase 3
Study of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein (FRSW107) On-Demand Treatment
Condition(s) studied
Severe Hemophilia A
Investigational drug(s) / intervention(s)
FRSW107
FRSW107: Treatment for 6 months as needed.
Study summary
The indication for this product is to control bleeding in patients with hemophilia A (congenital deficiency of factor VIII).
The primary objective:
Evaluation of the efficacy of recombinant human coagulation factor VIII-Fc fusion protein for injection (FRSW107) as an on-demand treatment in previously treated patients with severe hemophilia A.
Secondary objectives:
Evaluation of the safety and immunogenicity of FRSW107 as an on-demand therapy in previously treated patients with severe hemophilia A.
Evaluate the on-demand treatment's PK profile of FRSW107 in previously treated patients with severe hemophilia A based on population pharmacokinetic (PopPK) methods ; preliminarily investigate the exposure-response (E-R) relationship of FRSW107 on-demand treatment in these patients if data permit.
Eligibility
Inclusive Criteria:
1. Males aged 12 or younger to 65 years old.
2. Patients clinically diagnosed with severe hemophilia A, i.e., those confirmed through screening or previous medical records: FⅧ Activity \< 1%.
3. Previous records confirm receipt of any recombinant and/or blood-derived coagulation factor VIII products or cold precipitate products, with a treatment of ≥150 exposure days (EDs ≥150).
4. The participants have fully understood and been informed of this study, signed the informed consent form, and voluntarily enrolled in the clinical trial. The trial participants and/or their guardians are capable of cooperating with the hemostatic treatment 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. Patients with abnormal renal function:
Creatinine clearance (Ccr) \<50 ml/min (according to Cockcroft and Gault formula); or Serum creatinine (Cr) \>1.5x ULN;
9. People 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. Patients 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. Patients who have received transfusions of blood or blood components within 4 weeks prior to screening;
15. Participants who had participated in other 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 patients 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. Study patients who had used emesezumab within 6 months prior to first administration of the drug;
19. Patients who had used monoclonal antibody therapy, Fc fusion protein products (except FRSW107 and FRSW117), PEG products (except FRSW117), or intravenous immunoglobulin infusion within 3 months before the first administration of the investigational drug;
20. Study patients who underwent major surgery within 3 months prior to initial drug administration (major surgery is defined in 6.2.3 Perioperative management);
21. Study patients who have used FⅧ preparation of any standard half-life (e.g., Bycoch, Coproch, Biinidin, Renjie, NoL, Antaine, etc.) within 3 days or 5 half-lives prior to first administration of the drug (taking the elderly); Patients who have used any other extended half-life preparation FⅧ within 4 days or 5 half-lives prior to first dosing (for the elderly);
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)
- The haemostatic effective rate — 6 months
The haemostatic effect of FRSW107 when used for treatment of bleeds, assessed on a four-point scale for haemostatic response (excellent, good, moderate and none) by counting excellent and good as success and moderate and none as failure.
Trial sites (24)
| 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 |
|
| Ganzhou People's Hospital |
Ganzhou |
China |
|
| Nanfang Hospital of Southern Medical University |
Guangzhou |
China |
|
| Anhui Provincial Hospital |
Hefei |
China |
|
| Huai'an Second People's Hospital |
Huai'an |
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 |
|
| Rizhao People's Hospital |
Rizhao |
China |
|
| The Second Hospital of Hebei Medical University |
Shijiazhuang |
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 |
|
| Subei People's Hospital of Jiangsu province |
Yangzhou |
China |
|
| Henan Cancer Hospital |
Zhengzhou |
China |
|
| Zhengzhou People's Hospital |
Zhengzhou |
China |
|
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