Study of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein (FRSW107) as Prophylactic Treatment.

Official title

A Single-Arm, Open-Label, Multicenter Phase III Clinical Study Evaluating the Efficacy, Safety, Immunogenicity and Pharmacokinetics of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein (FRSW107) as Prophylactic Therapy in Patients With Severe Hemophilia A (Adults and Adolescents)

Overview

The indication for this product is to control and prophylaxis in patients with Hemophilia A (congenital Factor VIII deficiency): The Primary Objective： To evaluate the efficacy of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) for prophylactic treatment in previously treated patients with severe Hemophilia A. Secondary Objectives： To evaluate the health-related quality of life, pharmacokinetic (PK) profiles, safety and immunogenicity of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) for prophylactic treatment in previously treated subjects with severe Hemophilia A.

Interventions

• Drug FRSW107
  For subjects in the PK subgroup: they will receive a dose of 50 IU/kg at the first dose visit 1 to obtain preliminary pharmacokinetic (PK) data. After assessment by the investigator, individualized prophylactic treatment (25\~50 IU/kg, Q3D) will be administered to maintain the trough concentration of FVIII activity at ≥1%. For subjects not in the PK subgroup: they will receive prophylactic treatment at a dose of 25\~50 IU/kg once every three days. If a subject experiences a breakthrough bleedi

Primary outcome measures

• ABR [Time frame: 6 months]

Secondary outcome measures (12)

• Safety Evaluation [Time frame: 6 months]
• Immunogenicity Evaluation [Time frame: 6 months]
• Peak activity (Cmax) [Time frame: At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).]
• Effective rate of hemostatic treatment [Time frame: 6 months]
• Annualized rate of spontaneous bleeds and annualized rate of traumatic bleeds. [Time frame: 6 months]
• Annualized Joint Bleed Rate (AJBR) [Time frame: 6 months]
• Number of target joints. [Time frame: 6 months]
• Dosing parameters of prophylactic treatment [Time frame: 6 months]
• Factor VIII incremental recovery and trough levels during prophylactic treatment. [Time frame: 6 months]
• Time interval between each bleeding episode and the prior prophylactic dose during prophylaxis. [Time frame: 6 months]
• Dosing parameters for rescue hemostatic treatment of breakthrough bleeds during prophylaxis [Time frame: 6 months]
• Hemophilia Joint Health Score version 2.1 (HJHS 2.1) [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

1.12≤ age ≤65 year-old men; 2.Subjects with clinically confirmed severe hemophilia A, i.e. at screening (central laboratory testing) or previous medical records confirm: FⅧ activity < 1%; 3.Previous documented treatment with any recombinant and/or blood-derived coagulation factor Ⅷ products or cryoprecipitation products and dosed ≥150 exposure days (EDs≥150) ; 4.Normal prothrombin time (PT) or International Normalized Ratio (INR)<1.3; 5.Bleeding events were recorded in detail for at least 6 months prior to screening; 6.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

• Known or suspected allergy to the investigational drug or its excipients, including mouse or hamster proteins;
• Hypersensitivity or anaphylaxis after FⅧ or IgG2 injection in the past;
• 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;
• Von Willebrand factor (vWF) antigen test results were lower than the lower limit of normal value;
• Severe anemia at the screening stage (hemoglobin < 60 g/L);
• Platelet count during screening period < 100×109 /L;
• 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;
• Subjects with abnormal renal function: Creatinine clearance (Ccr) <50 ml/min (according to Cockcroft and Gault formula); or Serum creatinine (Cr) >1.5x ULN;
• Subjects 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);
• Subjects with coagulation dysfunction other than hemophilia A;
• Have a medical condition that may increase the risk of bleeding;
• A history of drug or alcohol abuse;
• Have a known mental disorder that may affect trial compliance;
• Subjects who have received transfusions of blood or blood components within 4 weeks prior to screening;
• Participants who had participated in other Interventional clinical trials within 1 month before screening;
• 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 subjects who need to be treated with anticoagulant or antiplatelet drugs or off-label maximum doses of SAID during clinical trials;
• 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.
• Subjects who have received emicizumab within 6 months prior to the first administration of study drug, or have previously received fitusiran (siRNA, brand name: CEPHEIN®) or gene therapy;
• Subjects who have received monoclonal antibody therapy, Fc fusion protein products, or intravenous immunoglobulin within 3 months prior to the first administration of study drug;
• Subjects who have undergone major surgery within 3 months prior to the first administration of study drug, or those who plan to receive surgery during the study period;
• Subjects who have received any standard half-life FⅧ preparations (e.g., Advate, Kovaltry, Octate, Recombinate, NovoEight, Anjiyin, etc.) within 3 days or 5 half-lives (whichever is longer) prior to the first administration of study drug; patients who have received any other extended half-life FⅧ preparations (e.g., Noxyte) within 4 days or 5 half-lives (whichever is longer) prior to the first administration of study drug;
• Study patients with fever, severe active bacterial or viral infection, and allergies within 2 weeks before the first administration of the drug;
• 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;
• 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);
• 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.);
• Have other serious medical conditions that the researchers said could not benefit from them
• Subjects deemed unsuitable by other investigators.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 19 centers

• Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Pe — Tianjin
• Fuyang Hospital, Affiliated to Anhui Medical University — Fuyang
• Fujian Medical University Union Hospital — Fuzhou
• Nanfang Hospital of Southern Medical University — Guangzhou
• Anhui Provincial Hospital — Hefei
• Jinan central hospital — Jinan
• The Second Affiliated Hospital of Kunming Medical University — Kunming
• The First Affiliated Hospital of Guangxi Medical University — Nanning
• … and 11 more centers

Identifiers

NCT: NCT07684898 · SS-107-III04

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗