Phase III Expansion Trial for Determining the Safety and Efficacy of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection in Adolescent and Adult Patients With Hemophilia A

Study Overview
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Brief Summary
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The primary objectives of the study are to further evaluate the efficacy and safety of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) in adolescent and adult patients with hemophilia A.

Official Title
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A Single-Arm, Multicenter, Open-label Phase III Expansion Trial Evaluating Safety and Efficacy of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) in Adolescent and Adult Patients With Hemophilia A

Conditions
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Hemophilia A

Intervention / Treatment
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* Drug: Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients Who have Completed trial of RH-107-001 (previously treated patients) Previously received Recombinant Human Coagulation Factor VIII-Fc prophylactic. The patient and/or guardian or his or her legal representative must be able to read, understand, and provide signed informed consent, And voluntarily signed the Informed Consent Form. The compliance of patients appeared quite well. Patient who is considered by the investigators suitable for ongoing to accept previously treated. Exclusion Criteria: Subjects who have not completed trial of RH-107-001or who have completed the Phase III clinical trial but not willing to continue receiving treatment. Subjects who did not participate in the Phase III clinical trial of RH-107-001.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Participants will receive prophylaxis treatment with Recombinant Human Coagulation Factor VIII-Fc fusion for 6 months. | Drug: Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection<br>* Participants received prophylaxis treatment at 50 IU/ kg every three days.30-50 IU/kg is recommended to administration while bleeding occurs during the experiment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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. | For the duration of study participation, 6 months. | 
| Number of target joints. | Describe the number and percentage of cases with target joints ≥1 and their 95% confidence intervals before and after drug administration, and compare the change in the number of target joints from baseline after treatment. | For the duration of study participation, 6 months. | 
| Annualized Joint Bleeding Rate (AJBR) | Annualized joint bleeding rate(AJBR)can be calculated using the following formula: Number of joint bleeding episodesevents during efficacy evaluation period/(number of days in treatment period/365.25). | For the duration of study participation, 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | For the duration of study participation, 6 months. | 
| 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. | For the duration of study participation, 6 months. | 
| Quality of life assessment. | Quality of life assessment by Haemophilia Joint Health Score(HJHS 2.1). | For the duration of study participation, 6 months. | 
| Score of bleeding symptoms and Vital signs. | Response to treatment with rFVIIIFc for bleeding episodes, using the 4-point bleeding response scale. | For the duration of study participation, 6 months. | 
| 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). | For the duration of study participation, 6 months. | 
| Number of Participants With Incidence of Antibody Formation to CHINESE HAMSTER OVARY (CHO). | A test to analyze the formation of antibodies to CHO. | For the duration of study participation, 6 months. | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events. (SAEs) as a Measure of Safety and Tolerability. | An AE is any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition. | For the duration of study participation, 6 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia A, Factor VIII-Fc Fusion Protein, Phase III Expansion Trial, Efficacy and Safety