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

NCT ID: NCT04864743

Last Updated: 2023-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-22
• Study Completion Date: 2021-10-17

Brief Summary

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

Conditions

Severe Hemophilia A

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

ADVATE

Intervention Type: DRUG

a single dose.

FRSW117

Intervention Type: DRUG

a single dose.

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

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.

Group Type: EXPERIMENTAL

ADVATE

Intervention Type: DRUG

a single dose.

FRSW117

Intervention Type: DRUG

a single dose.

Interventions

ADVATE

a single dose.

Intervention Type: DRUG

FRSW117

a single dose.

Intervention Type: DRUG

Other Intervention Names

PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection

Eligibility Criteria

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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu Gensciences lnc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Renchi Yang, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College.

Locations

Nanfang Hospital of Southern Medical University

Guangzhou, Guangzhou, China

People's Hospital of Zhengzhou

Zhengzhou, Henan, China

Jinan central hospital

Jinan, Shandong, China

Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College.

Tianjin, Tianjin Municipality, China

Countries

China

Other Identifiers

CTR20210830

Identifier Type: -

Identifier Source: org_study_id