Evaluating a new treatment for severe hemophilia A

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)

This study is testing a new treatment for people with severe hemophilia A to see if it can help prevent bleeding and be safe to use.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 12 Years to 65 Years
• Sex: Male
• Sponsor: Jiangsu Gensciences lnc. (Industry-sponsored)
• Drugs / interventions: emesezumab, cyclophosphamide, prednisone
• Locations: 28 sites (Beijing and 27 other locations)
• Trial ID: NCT06142552 on ClinicalTrials.gov

What this trial studies

This clinical project aims to assess the prophylactic efficacy and safety of a pegylated recombinant human coagulation factor VIII-Fc fusion protein (FRSW117) in patients with severe hemophilia A. The study will evaluate the drug's effectiveness in preventing bleeding episodes and its pharmacokinetic characteristics. Additionally, it will investigate the immunogenicity of the treatment and its efficacy in surgical hemostasis. Participants will be closely monitored for bleeding events and overall response to the treatment.

Who should consider this trial

Good fit: Ideal candidates are men aged 12 to 65 with clinically confirmed severe hemophilia A and a history of significant bleeding episodes.

Not a fit: Patients with known or suspected allergies to the investigational product will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce bleeding episodes and improve quality of life for patients with severe hemophilia A.

How similar studies have performed: Other studies have shown promise with similar recombinant factor therapies, indicating potential for success with this approach.

Eligibility criteria

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: FⅧ activity \< 1%；
* Previous documented treatment with any recombinant and/or blood-derived coagulation factor Ⅷ 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 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 \&lt; 60 g/L);
6. Platelet count during screening period \&lt; 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 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.

Where this trial is running

Beijing and 27 other locations

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

Study contacts

• Study coordinator: Chen Ling

Conditions Severe Hemophilia A; Pharmacokinetics; Safety; immunogenicity; effectiveness