A Study to Evaluate the Pharmacokinetics 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 at two dose levels in patients with hemophilia A. Secondary objectives: To assess Safety and Tolerability by monitoring FVIII recovery and adverse events in patients with hemophilia A.

Official Title
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A Phase I, Multicentre, Open-label, Self-control Study to Evaluate the Pharmacokinetics of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection in Adolescent and Adult Patients With 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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Inclusion Criteria: 12 years to 60 years, male. The activity of the coagulation factor VIII (FVIII:C) < 2%, and previously treated with FVIII concentrate (s) for a minimum of 150 exposure days (EDs) prior to study entry. Non-immune deficiency (CD4 > 200/μL). Non-acute hemorrhagic state. No history of a positive inhibitor test (< 0.6 BU) or clinical signs of decreased response to FVIII administrations. No Family history of inhibitors. Platelet count > 100,000 platelets/μL. Normal prothrombin time or INR < 1.3. Normal thrombin time (TT). Normal previous results of vWF antigen examination. Negative lupus anticoagulant . Capable of understanding and willing to comply with the conditions of the protocol have read (patient and/or guardian). 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 IgG2 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 4 days prior screening or within 72 h prior to administration. Patients with severe heart disease, including myocardial infarction, heart failure (III or higher level). Clinically significant of other systematic diseases: alcoholism, drug abuse, mental disorders and mental retardation. Significant hepatic or renal impairment (ALT and AST > 2×ULN; serum bilirubin level > 3 × upper limit of normal (ULN) , BUN > 2×ULN, Cr > 2.0 mg/dL). 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 1 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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 60 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Arm 1<br>Participants will receive a single intravenous (i.v.) injection of ADVATE followed by a single intravenous (i.v.) injection of Recombinant Human Coagulation Factor VIII-Fc fusion protein for Injection (FRSW107) at a low dose. | Drug: ADVATE<br>* Patients will be administered a single dose of ADVATE.<br>Drug: FRSW107<br>* Patients will be administered a single dose of FRSW107 for Injection.<br>|
| Arm 2<br>Participants will receive a single intravenous (i.v.) injection of ADVATE followed by a single intravenous (i.v.) injection of Recombinant Human Coagulation Factor VIII-Fc fusion protein for Injection (FRSW107) at a high dose. | Drug: ADVATE<br>* Patients will be administered a single dose of ADVATE.<br>Drug: FRSW107<br>* Patients will be administered a single dose of FRSW107 for Injection.<br>|

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 the One-stage aPTT Clotting Assay. | Pre-dose and post dose of FRSW107 up to 10 days. | 
| Time required for the concentration of the drug to reach half of its original value (T1/2). | Measured by the One-stage aPTT Clotting Assay. | Pre-dose and post dose of FRSW107 up to 10 days. | 
| Area Under the Curve to Infinity (AUC). | Measured by the One-stage aPTT Clotting Assay. | Pre-dose and post dose of FRSW107 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 the One-stage aPTT Clotting Assay. | Pre-dose and post dose of FRSW107 up to 10 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 of FRSW107 up to 28. | 
| Development of Inhibitor. | Measured by the Nijmegen-Modified Bethesda Assay. | Pre-dose and post dose of FRSW107 up to 28 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia A, Pharmacokinetics, Factor VIII-Fc Fusion Protein, Adolescent and Adult Patients, Phase I, Safety and Tolerability