Phase 3 Clinical Project of Pegylated Recombinant Human Coagulation Factor VIII-Fc Fusion Protein

Severe Hemophilia A Clinical Trial

Official title:

Multicenter Study to Evaluate the Efficacy, Safety, Immunogenicity, and Pharmacokinetics of Recombinant Human Coagulation Factor Ⅷ-Fc Fusion Protein (FRSW117) for Injection in Patients With Severe Hemophilia A (Adults and Adolescents)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06142552
• Other study ID #: SS-117-III01
• Status: Recruiting
• Phase: Phase 3
• Start date: December 27, 2023
• Est. completion date: September 1, 2026

Study information

• Verified date: February 2024
• Source: Jiangsu Gensciences lnc.
• Contact: Chen Ling
• Phone: + 86 15896762713
• Email: chenling[@]gensciences.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the prophylactic efficacy of recombinant human coagulation factor Ⅷ-Fc fusion protein (FRSW117) for injection in patients with severe hemophilia A. To evaluate the safety of recombinant human coagulation factor Ⅷ-Fc fusion protein (FRSW117) for injection in patients with severe hemophilia A. Secondary purpose: To evaluate the efficacy of recombinant human coagulation factor Ⅷ-Fc fusion protein for injection (FRSW117) in hemostasis and surgical hemostasis in patients with severe hemophilia A. To evaluate the pharmacokinetic (PK) characteristics of recombinant human coagulation factor Ⅷ-Fc fusion protein (FRSW117) for injection in treated patients with severe hemophilia A. To evaluate the immunogenicity of recombinant human coagulation factor Ⅷ-Fc fusion protein (FRSW117) for injection in treated patients with severe hemophilia A.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: September 1, 2026
• Est. primary completion date: January 15, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 65 Years

Eligibility

inclusion Criteria:

• 12= age =65 year-old men;
• Patients with clinically confirmed severe hemophilia A, i.e. at screening (central laboratory testing) or previous medical records confirm: F? activity < 1%;
• Previous documented treatment with any recombinant and/or blood-derived coagulation factor ? products or cryoprecipitation products and dosed =150 exposure days (EDs=150)
• Normal prothrombin time (PT) or International Normalized Ratio (INR)<1.3
• Bleeding events were recorded in detail for at least 6 months prior to screening(Participants in the on demand /PPX group were required to have at least 6 episodes of spontaneous bleeding within 6 months)
• 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 F? or IgG2 injection in the past;

3. F? inhibitor positive (=0.6 BU/mL) during the screening period, or have a history of F? inhibitor positive in the past, or a family history of F? 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); orSerum 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 F? 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 F? 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.

Related Conditions & MeSH terms

• Hemophilia A
• Severe Hemophilia A

Intervention

Drug:
• FRSW117
once a week, 50 weeks and as needed

Locations

Country	Name	City	State
China	Beijing tongren hospital,CMU	Beijing
China	XiangYa Hospital CentralSouth University	Changsha
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing
China	Fujian Medical University Union Hospital	Fuzhou
China	Nanfang Hospital of Southern Medical University	Guangzhou
China	The First Affiliated Hospital,Zhejiang University School of Medicine	Hangzhou
China	Anhui Provincial Hospital	Hefei
China	Jinan central hospital	Jinan
China	The First Affiliated Hospital of Shandong First Medical University	Jinan
China	The Second Affiliated Hospital of Kunming Medical University	Kunming
China	The First Hospital of Lanzhou University	Lanzhou
China	Jiangxi Provincial People's Hospital	Nanchang
China	Nanjing Drum Tower Hospital	Nanjing
China	Affiliated Hospital of Nantong University	Nantong
China	The Affiliated Hospital of Qingdao University	Qingdao
China	Ruijin Hospital, Shanghai Jiaotong University School Of Medicine	Shanghai
China	Shenzhen Second People's Hospital	Shenzhen
China	The First Affiliated Hospital of Soochow University	Suzhou
China	The Second Hospital of Shanxi Medical University	Taiyuan
China	North China University of Science and Technology Affiliated Hospital	Tangshan
China	Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College	Tianjin
China	Affiliated Hospital of Jiangnan University	Wuxi
China	The First Affiliated Hospital of Xiamen University	Xiamen
China	Zhenyu Li	Xuzhou
China	Subei People's Hospital of Jiangsu province	Yangzhou
China	Henan Cancer Hospital	Zhengzhou
China	Henan Provincial People's Hospital	Zhengzhou
China	Zhengzhou People's Hospital	Zhengzhou

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Gensciences lnc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ABR	Annual rate of bleeding (ABR) during preventive treatment = Number of bleeding during the efficacy evaluation period/(number of treatment days /365.25)	1year
Primary	Effective rate of bleeding treatment	The hemostatic effect was evaluated according to a four-level scoring scale, including breakthrough bleeding treatment during preventive treatment and on-demand treatment during on-demand treatment	2year
Primary	Safety evaluation	Incidence of positive F? inhibitor.; Adverse events/Adverse events: Adverse events during treatment (TEAE), serious Adverse events (SAEs), adverse events of particular concern (AESI), occurrences of adverse events that cause subjects to discontinue medication, drop out of the study, and death, and occurrences of the above metrics associated with the investigational drug.; Injection site reaction.; Laboratory tests: blood routine, urine routine, blood biochemistry, coagulation function, virology and immune function tests.; Thrombosis markers.; Vital signs, physical examination, neurological examination, 12-lead electrocardiogram, surgery-related complications.; PEG level.	3year
Primary	Adverse events/reactions	Adverse events during treatment (TEAE), serious Adverse events (SAEs), with a special focus on adverse events (AESI), adverse events that cause subjects to discontinue medication, drop out of the study, and die, etc.	ALL
Primary	Immunogenicity evaluation	The positive rate of anti-FRSW117 antibody, anti-PEG antibody and anti-CHO antibody; When the anti-FRSW117 antibody was positive, the anti-RHFVIII antibody and anti-PEG antibody were further detected to evaluate the positive incidence	ALL