A Study to Evaluate the Safety and Pharmacokinetic of Recombinant Human Coagulation Factor VIII ，Fc Fusion Protein for Injection

Study Overview
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Brief Summary
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Primary objective: To assess the pharmacokinetics of Recombinant Human Coagulation Factor VIII, Fc Fusion Protein for Injection (FRSW107) Secondary objectives: To assess Safety and Tolerability by monitoring FVIII recovery and adverse events in Severe Hemophilia A.

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

Conditions
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Hemophilia A

Intervention / Treatment
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* Drug: ADVATE
* Drug: FRSW107


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: The activity of the coagulation factor VIII (FVIII:C) < 1%. Less than 6 years old Patients previously treated with FVIII concentrate (s) for a minimum of 50 exposure days (EDs) prior to study entry. 6 years old to 12 years old 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. Infusion of any products containing FVIII within 72 h prior to administration. Significant hepatic or renal impairment (ALT and AST > 2×ULN; serum bilirubin level > 2 × upper limit of normal (ULN), BUN > 2×ULN, Cr > 2.0 ULN). 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 to administration. 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.

Ages Eligible for Study
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Maximum 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>Subjects(up to 12 years of age) received two treatments: 50 IU/kg ADVATE in the first period, followed by 50 IU/kg FRSW107 in the second period. | Drug: ADVATE<br>* 50 international units (IU)/kg, a single dose.<br>Drug: FRSW107<br>* 50 IU/kg, a single dose.<br>* Other names: Recombinant Human Coagulation Factor VIII, Fc Fusion Protein for Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum measured concentration of FVIII:C (Cmax) | Measured by aPTT Clotting Assay. | Pre-dose and post dose up to 8 days. | 
| Time required for the concentration of the drug to reach half of its original value (T1/2) | Measured by aPTT Clotting Assay. | Pre-dose and post dose up to 8 days | 
| Area Under the Curve to Infinity (AUC) | Measured by aPTT Clotting Assay. | Pre-dose and post dose up to 8 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 aPTT Clotting Assay. | Pre-dose and post dose up to 8 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 Recombinant Human Coagulation Factor VIII-Fc fusion protein for Injection according to Common Terminology Criteria for Adverse Events (CTCAE) NCI.V5.0. | Post dose up to 32 days. | 
| Development of Inhibitor | Measured by the Nijmegen-Modified Bethesda Assay. | Pre-dose and post dose up to 32 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia A;Pharmacokinetics;Child;Safety and Tolerability