The primary objectives of the study are to evaluate the efficacy of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) in the Prevention and Treatment of Bleeding in patients with hemophilia A. The secondary objectives are to evaluate the efficacy and safety of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) in the prevention and treatment of bleeding episodes, to investigate the quality of life in patients who used the FRSW107.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
119
Participants received on-demand treatment, doses range from 30 IU/kg to 50 IU/kg, or doses divided on the discretion of the Investigator.
Participants received prophylaxis treatment at 50 IU/kg every three days.
Anhui Provincial Hospital
Hefei, Anhui, China
Capital Medical University affiliated Beijing Children's Hospital
Beijing, Beijing Municipality, China
Chongqing Three Gorges Central Hospital
Chongqing, Chongqing Municipality, China
Fujian Medical University Union Hospital
Fuzhou, Fujian, China
The First Hospital of Lanzhou University
Lanzhou, Gansu, China
The Second Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, China
Nanfang Hospital of Southern Medical University
Guangzhou, Guangzhou, China
The Affiliated Hospital of Guizhou Medical University
Guiyang, Guizhou, China
Henan provincial People's Hospital
Zhengzhou, He'nan, China
Henan Cancer Hospital
Zhengzhou, He'nan, China
...and 7 more locations
Part A - score of bleeding symptoms and Vital signs.
Response to treatment with rFVIIIFc for bleeding episodes, using the 4-point bleeding response scale.
Time frame: For the duration of study participation, 6 months.
Part B- Annualized Bleeding Rates(ABR).
Annualized bleeding rate = (number of bleeding episodes during the efficacy, period/total number of days during the efficacy period)\*365.25. The efficacy period begins with the first prophylactic dose of FRSW107 and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. A bleeding episode started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, within which any symptoms of bleeding at the same location or injections less than or equal to 72 hours apart were considered the same bleeding episode. Any injection to treat the bleeding episode taken more than 72 hours after the preceding one was considered the first injection to treat a new bleeding episode at the same location. Any bleeding at a different location was considered a separate bleeding episode, regardless of time from last injection.
Time frame: For the duration of study participation, 6 months.
Part B-Number of target joints.
The joint with ≥3 times of spontaneous bleeding in 6 consecutive months is the target joint, while the joint with \< 2 times of bleeding in 12 consecutive months is no longer the target joint.
Time frame: For the duration of study participation, 6 months.
Part A-rFVIIIFc incremental recovery (IR).
Incremental recovery of Factor VIII (FVIII) within 1 hour after end of infusions was determined and mean recovery values were reported.
Time frame: For the duration of study participation, 6 months.
Part A -Total Dose Required for Resolution of a Bleeding Episode.
The total dose required to resolve a bleeding episode per participant, based on the efficacy period. The efficacy period begins with the first dose and ends with the last dose (for a bleed). For 'Per bleeding episode' values, for each bleeding episode, the total dose is the sum of the doses (IU/kg) administered across all injections given to treat that bleeding episode. For 'Per participant' values, the total dose (IU/kg) used to resolve each bleed is averaged across all bleeding episodes per participant.Quality of life assessment.
Time frame: For the duration of study participation, 6 months.
Part A -Number of injections required to resolve a bleeding episode.
The number of injections required to resolve a bleeding episode per participant, based on the efficacy period. The efficacy period begins with the first dose and ends with the last dose (for a bleed). All injections given from the initial sign of a bleed, until the last date/time within the bleed window are counted. The resolution of a bleed is defined as no sign of bleeding following injection for the bleed. For 'Per participant' values, the number of injections required to resolve each bleed is averaged across all bleeding episodes per participant.
Time frame: For the duration of study participation, 6 months.
Part A -Quality of life assessment.
Quality of life assessment by Haemophilia Joint Health Score（HJHS）.
Time frame: For the duration of study participation, 6 months.
Part B -Number of injections required to resolve a bleeding episode.
The number of injections required to resolve a bleeding episode per participant, based on the efficacy period. The efficacy period begins with the first prophylactic dose and ends with the last dose (for prophylaxis or a bleed). All injections given from the initial sign of a bleed, until the last date/time within the bleed window are counted. The resolution of a bleed is defined as no sign of bleeding following injection for the bleed. For 'Per participant' values, the number of injections required to resolve each bleed is averaged across all bleeding episodes per participant.
Time frame: For the duration of study participation, 6 months.
Part B -Quality of life assessment.
Quality of life assessment by Haemophilia Joint Health Score(HJHS).
Time frame: For the duration of study participation, 6 months.
Part B -Number of participants with inhibitor development
Number of participants who developed a positive FVIII inhibitor level (≥0.6 Bethesda unit \[BU\]) during the study was summarized and classified as participants developing low titer inhibitor (i.e. ≤ 5.0 BU) and participants developing high titer inhibitor (i.e. \> 5.0 BU).
Time frame: 6 months and at least 50 exposure days.
Part B - Number of Participants With Incidence of Antibody Formation to CHINESE HAMSTER OVARY (CHO).
A test to analyze the formation of antibodies to CHO.
Time frame: before and the duration of study participation, 6 months.
Part B -Number of All Bleeds.
The annualized number of bleeds experienced by participants.
Time frame: before and the duration of study participation, 6 months.
Part B-Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay
Maximum measured concentration of rFVIIIFc.
Time frame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
Part B-Half-life (t½) as Measured by aPTT Clotting Assay
Time required for the concentration of the drug to reach half of its original value.
Time frame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
Part B-Clearance (CL) as Measured by the aPTT Clotting Assay
The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time.
Time frame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
Part B-Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay.
The apparent volume of distribution at steady state. (Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.).
Time frame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
Part B-Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay.
The average time at which the number of absorbed molecules reside in the body, after single-dose administration.
Time frame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
Part B-Time of Cmax (Tmax) as Measured by aPTT Clotting Assay.
Time at which maximum activity (Cmax) is observed.
Time frame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
Part B-Area Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay.
Area under the plasma concentration time-curve from zero to the last measured concentration.
Time frame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
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