A Study to Evaluate the Pharmacokinetics，Safety and Tolerability of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection

Jiangsu Gensciences

Status and phase: Completed; Phase 1

Conditions: Severe Hemophilia A

Treatments: Drug: FRSW117; Drug: ADVATE

Study type: Interventional

Funder types: Industry

Identifiers

NCT04864743

CTR20210830

Details and patient eligibility

About

The primary objectives of the study are to evaluate the Pharmacokinetics，Safety and tolerability of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW117) in patients with severe hemophilia A.

The secondary objectives are to monitor anti-durg antibodies and anti-PEG antibodies levels in patients with severe hemophilia A

Enrollment: 13 patients

Sex: Male

Ages: 12 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with clinically confirmed hemophilia A (coagulation factor VIII <1%) and previous medical records confirming exposure to coagulation factor VIII for ≥150 days (EDs ≥150).
• Non-immunodeficient, with some immunity (CD4 > 200/μL).
• Platelet count >100×10^9/L.
• Normal prothrombin time (PT) or international normalized ratio (INR) <1.3.
• Negative lupus anticoagulant.
• Fully understand, informed about this study and sign the informed consent form, voluntarily participate in the clinical study and have the ability to complete all study procedures

Exclusion criteria

• Hypersensitivity to the test substance or its excipients (including rodent or hamster protein).
• Pre-existing hypersensitivity or allergic reactions to FVIII or IgG2 injection therapy.
• Positive FVIII inhibitor at screening (≥0.6 BU/mL), or previous history of FVIII inhibitor Positive history, or family history of inhibitors.
• Patients with other coagulation disorders in addition to hemophilia A.
• The results of vWF antigen examination lower than normal.
• Severe anemia and need blood transfusion (hemoglobin < 60g/L).
• Patients who have received any standard half-lives FVIII formulations (e.g., Kogenate, Kovaltry, Advate, Xyntha, etc.) or received any other half-life-extending FVIII formulations within 4 days or 5 half-lives (whichever is longer) before administration.
• Patients who had used emecizumab within 6 months prior to administration.
• Patients with fever, upper respiratory tract infection or allergy symptoms within the previous 2 weeks before screening.
• Suffer from other diseases that may increase the risk of bleeding or the risk of thrombosis.
• Severe cardiovascular and cerebrovascular diseases: such as cerebral hemorrhage, stroke, myocardial infarction, unstable angina pectoris, congestive heart failure(the current New York Heart Association cardiac function grade III, Hypertension that cannot be controlled with drug treatment: systolic blood pressure> 160 mmHg or diastolic blood pressure> 95 mmHg.
• 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)).
• Abnormal kidney function: BUN > 2×ULN, Cr > 2.0mg/dL.
• One or more clinically significant tests for Hepatitis B Virus Surface Antigen, Human Immunodeficiency Virus (HIV), Antisyphilitic spirulina (TPHA) and Hepatitis C Virus (HCV) Antibody.
• Patients who received any anticoagulant or antiplatelet therapy within a week prior screening or need to receive an anticoagulant or antiplatelet therapy during the period of clinical trials.
• Systemic immunomodulators (e.g., corticosteroids [equivalent dose of 10 mg/ day prednisone], A-interferon, immunoglobulin, cyclophosphamide, cyclosporine, etc.) were used within 14 days prior to administration or during the study period.
• Patients having major surgery or receiving blood or blood 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 a 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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13 participants in 2 patient groups

Arm 1-ADVATE+FRSW117(25 IU/kg)

Experimental group

Description:

Subjects received two treatments: 25 IU/kg ADVATE in the first period, followed by 25 IU/kg FRSW117 in the second period, with a washout period before each treatment.

Treatment:

Drug: FRSW117

Drug: ADVATE

Arm 2-ADVATE+FRSW117( 50 IU/kg)

Experimental group

Description:

Subjects received two treatments: 50 IU/kg ADVATE in the first period, followed by 50 IU/kg FRSW117 in the second period, with a washout period before each treatment.

Treatment:

Drug: FRSW117

Drug: ADVATE