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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
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 bleeding episode requiring treatment, the investigator shall determine the appropriate dosage (recommended dose range: 20\~50 IU/kg) and administration frequency.
Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
Tianjin, Tianjin Municipality, China
Fuyang Hospital, Affiliated to Anhui Medical University
Fuyang, China
Fujian Medical University Union Hospital
Fuzhou, China
Nanfang Hospital of Southern Medical University
Guangzhou, China
Anhui Provincial Hospital
Hefei, China
Jinan central hospital
Jinan, China
The Second Affiliated Hospital of Kunming Medical University
Kunming, China
The First Affiliated Hospital of Guangxi Medical University
Nanning, China
Affiliated Hospital of Nantong University
Nantong, China
The First Affiliated Hospital of Nanyang Medical College
Nanyang, China
...and 9 more locations
ABR
Annual rate of bleeding (ABR) during preventive treatment = Number of bleeding episode during the efficacy evaluation period/(number of treatment days /365.25)
Time frame: 6 months
Safety Evaluation
Incidence of positive FⅧ inhibitor (key secondary endpoint)
Time frame: 6 months
Immunogenicity Evaluation
Incidence of positive anti-FRSW107 antibodies and anti-CHO antibodies; for subjects with positive anti-FRSW107 antibodies, additional testing for anti-rhFVIII antibodies shall be performed to assess their positive incidence.
Time frame: 6 months
Peak activity (Cmax)
Applicable to PK Subgroup: 1. Single administration: Peak activity (Cmax). 2. Multiple administrations: Cmax.
Time frame: At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
Effective rate of hemostatic treatment
During the prophylactic treatment period, breakthrough hemostatic therapy was evaluated based on a four-level scoring scale (excellent, good, moderate, ineffective), with scores of "excellent" or "good" indicating efficacy.
Time frame: 6 months
Annualized rate of spontaneous bleeds and annualized rate of traumatic bleeds.
Annualized rate of spontaneous bleeds and annualized rate of traumatic bleeds.
Time frame: 6 months
Annualized Joint Bleed Rate (AJBR)
Annualized Joint Bleed Rate (AJBR), including overall AJBR, annualized rate of spontaneous joint bleeds and annualized rate of traumatic joint bleeds. AJBR = Number of joint bleeds during efficacy evaluation period / (Number of treatment days / 365.25).
Time frame: 6 months
Number of target joints.
Number of target joints. Target joint definition: A joint with ≥3 spontaneous bleeds within any consecutive 6 months is defined as a target joint; a joint will no longer be classified as a target joint if it experiences ≤2 bleeds within any consecutive 12 months.
Time frame: 6 months
Dosing parameters of prophylactic treatment
Dosing parameters of prophylactic treatment: total cumulative dose during study, annual total dose, mean dose per prophylactic administration; administration frequency: total number of injections, mean annual injection frequency; dosing interval: mean interval between prophylactic administrations throughout the prophylaxis period.
Time frame: 6 months
Factor VIII incremental recovery and trough levels during prophylactic treatment.
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 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
Dosing parameters for rescue hemostatic treatment of breakthrough bleeds during prophylaxis: mean dose, total cumulative dose and total number of administrations.
Time frame: 6 months
Hemophilia Joint Health Score version 2.1 (HJHS 2.1)
Hemophilia Joint Health Score version 2.1 (HJHS 2.1): total HJHS 2.1 score, individual domain subscores, and their respective changes from baseline.
Time frame: 6 months
EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) and EuroQol Visual Analogue Scale (EQ VAS) .
EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) and EuroQol Visual Analogue Scale (EQ VAS), together with their changes from baseline.The total healthy utility index score ranges of EQ-5D-5L from a minimum value of 0 points to a maximum value of 1 points,higher scores mean a better outcome.The total score ranges of EuroQol Visual Analogue Scale (EQ VAS) from a minimum value of 0 points to a maximum value of 100 points,higher scores mean a better outcome.
Time frame: 6 months
Incidence of insufficient therapeutic response
Incidence of insufficient therapeutic response.
Time frame: 6 months
time to peak (Tmax)
Applicable to PK Subgroup: 1. Single administration: time to peak (Tmax). 2. Multiple administrations: Tmax.
Time frame: At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
area under the concentration-time curve from time zero to the last quantifiable time point (AUC₀-ₗₐₛₜ)
Applicable to PK Subgroup: 1. Single administration: area under the concentration-time curve from time zero to the last quantifiable time point (AUC₀-ₗₐₛₜ). 2. Multiple administrations: AUC₀-ₗₐₛₜ.
Time frame: At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
elimination half-life (t₁/₂)
elimination half-life (t₁/₂)
Time frame: At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
incremental recovery
incremental recovery (calculated based on FⅧ Cmax measured after the end of infusion, unit: \[IU/dL\]/\[IU/kg\])
Time frame: At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
The time for FⅧ activity to decline to 15%, 5%, 3% and 1% .
The time for FⅧ activity to decline to 15%, 5%, 3% and 1% respectively after study drug infusion.
Time frame: At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
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