A Study of Repeat Dosing of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection

Study Overview
=================
Brief Summary
-----------------
Primary objective: To assess the pharmacokinetics, Safety and immunogenicity of Repeat Dosing of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection With Severe Hemophilia A(FRSW117) Secondary objectives: To assess Preliminary efficacy of Repeat Dosing of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection With Severe Hemophilia A.

Official Title
-----------------
A Phase II, Multicentre, Open-label Study to Evaluate the Pharmacokinetic, Safety and Preliminary Efficacy of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection in Subjects With Severe Hemophilia A

Conditions
-----------------
Severe Hemophilia A

Intervention / Treatment
-----------------
* Drug: FRSW117


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: The activity of the coagulation factor VIII (FVIII:C) < 1%. Patients previously treated with FVIII concentrate (s) for a minimum of 150 exposure days (EDs) prior to study entry Normal prothrombin time or INR < 1.3 Negative lupus anticoagulant Key Exclusion Criteria: Hypersensitive to any of the excipients of the test materials (e.g. allergic to murine or hamster origin heterologous proteins) History of hypersensitivity or anaphylaxis associated with any FVIII or II immunoglobulin administration Current FVIII inhibitor-positive or history of FVIII inhibitor-positive Other coagulation disorder(s) in addition to hemophilia A.• Significant hepatic or renal impairment (ALT and AST > 2×ULN; serum bilirubin level > 2 × upper limit of normal (ULN), Urea /BUN > 2×ULN, Cr > 176.8 µmol/L) One or more clinically significant tests for Human Immunodeficiency Virus (HIV), Antisyphilitic spirulina (TPHA) and Hepatitis C Virus (HCV) Antibody Patients who received any anticoagulant or antiplatelet therapy within one week prior screening or need to receive an anticoagulant or antiplatelet therapy during the period of clinical trials Patients having major surgery or receiving blood or bood components transfusion within 4 weeks prior screening or having planned major surgery schedule during the study Patients who previously participated in the other clinical trials within one month prior screening Any life-threatening disease or condition which, according to the investigator's judgment, could not benefit from the trial participation Patient who is considered by the other investigators not suitable for clinical study Other protocol-defined inclusion/exclusion Criteria May Apply.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 prophylaxis treatment<br>Subjects of high dose group are being received four doses of FRSW117. dosing on day1(ED1), day8(ED2), day15(ED3), day22(ED4) respectively. Subjects of low dose group are being received four doses of FRSW117. dosing on day1(ED1), day8(ED2), day15(ED3), day22(ED4) respectively. All subjects are being received PK assessment in ED1 and ED4. | Drug: FRSW117<br>* Subjects of high dose group are being received four doses(50 IU/kg,once a week or every 7 days) of FRSW117. Subjects of low dose group (40 IU/kg,once a week or every 7 days)are being received four doses of FRSW117.<br>* Other names: PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum measured concentration of FVIII:C (Cmax) | Measured by One-Stage Clotting Assay | Pre-dose and post dose up to 10 days | 
| Time required for the concentration of the drug to reach half of its original value (T1/2) | Measured by One-Stage Clotting Assay | Pre-dose and post dose up to 10 days | 
| Area Under the Curve to Infinity (AUC) | Measured by One-Stage Clotting Assay | Pre-dose and post dose up to 10 days | 
| 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 (CL) | Measured by One-Stage Clotting Assay | Pre-dose and post dose up to 10 days | 
| Evaluation of the level of anti-PEG-rFⅧFc antibody production in participants |  | Pre-dose and post dose up to 36 days | 
| Evaluation of the level of anti-PEG antibody production in participants |  | Pre-dose and post dose up to 36 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE V5.0 | Adverse events related to PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein according to Common Terminology Criteria for Adverse Events (CTCAE) NCI.V5.0. | Pre-dose and post dose up to 36 days | 
| Development of Inhibitor | Measured by the Nijmegen-Modified Bethesda Assay | Pre-dose and post dose up to 36 days | 
| score of bleeding symptoms and Vital signs | Response to treatment with PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for bleeding episodes, using the 4-point bleeding response scale | Pre-dose and post dose up to 36 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pharmacokinetics;, Safety;, immunogenicity;, Preliminary efficacy