Clinical trial NCT06142552: Phase 3 Clinical Project of Pegylated Recombinant Human Coagulation Factor VIII-Fc Fusion Protein
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Severe Hemophilia A
Keywords: Pharmacokinetics
Safety
immunogenicity
effectiveness
Lead sponsor: Jiangsu Gensciences lnc.
Sponsor class: INDUSTRY
First posted: 2023-11-21
Enrollment: 120
Sex: MALE
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


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.

Primary outcomes:
measure: ABR
timeFrame: 1year
measure: Effective rate of bleeding treatment
timeFrame: 2year
measure: Safety evaluation
timeFrame: 3year
measure: Adverse events/reactions
timeFrame: ALL
measure: Immunogenicity evaluation
timeFrame: ALL
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing tongren hospital,CMU
city: Changsha
country: China
facility: XiangYa Hospital CentralSouth University
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
city: Hangzhou
country: China
facility: The First Affiliated Hospital，Zhejiang University School of Medicine
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Jinan
country: China
facility: Jinan central hospital
city: Jinan
country: China
facility: The First Affiliated Hospital of Shandong First Medical University
city: Kunming
country: China
facility: The Second Affiliated Hospital of Kunming Medical University
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
city: Nantong
country: China
facility: Affiliated Hospital of Nantong University
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School Of Medicine
city: Shenzhen
country: China
facility: Shenzhen Second People's Hospital
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi Medical University
city: Tangshan
country: China
facility: North China University of Science and Technology Affiliated Hospital
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
city: Wuxi
country: China
facility: Affiliated Hospital of Jiangnan University
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Xuzhou
country: China
facility: Zhenyu Li
city: Yangzhou
country: China
facility: Subei People's Hospital of Jiangsu province
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
city: Zhengzhou
country: China
facility: Zhengzhou People's Hospital
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College.
name: Renchi Yang
role: STUDY_CHAIR
References: