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

Jiangsu Gensciences

Status and phase: Enrolling; Phase 3

Conditions: Severe Hemophilia A

Treatments: Drug: FRSW117

Study type: Interventional

Funder types: Industry

Identifiers

NCT06142552

SS-117-III01

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: Male

Ages: 12 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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120 participants in 3 patient groups

Prevention and Treatment Group (PPX group)

Experimental group

Description:

Subjects received single and multiple doses of 50 IU/kg FRSW117 at first administration of V1 (D1), V4 (18w), and V7 (50w), and PK samples were collected until 168 h post-administration, respectively. During prophylaxis, FRSW117 is used for breakthrough therapy if the subject has a breakthrough bleeding event (i.e., a bleeding event during prophylaxis) that requires treatment.

Treatment:

Drug: FRSW117

On Demand/Preventive Treatment Group (On Demand /PPX Group)

Experimental group

Description:

The appropriate dose and frequency of administration of FRSW117 is recommended until bleeding events are controlled or returned to pre-bleeding activity.

Treatment:

Drug: FRSW117

Perioperative management

Experimental group

Description:

Patients in the PPX and on demand /PPX groups will be allowed to undergo surgery (both major and minor) during the main trial period (prior to 50w), while FRSW117 will be administered perioperatively

Treatment:

Drug: FRSW117