An Open-Label, Multicenter Evaluation of the Pharmacokinetics，Safety and Tolerability of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW117) in Patients With Severe Hemophilia A.
Overview
- Phase
- Phase 1
- Intervention
- ADVATE
- Conditions
- Severe Hemophilia A
- Sponsor
- Jiangsu Gensciences lnc.
- Enrollment
- 13
- Locations
- 4
- Primary Endpoint
- Arm1 - T½ from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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
Investigators
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.
- •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.
Arms & Interventions
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.
Intervention: ADVATE
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.
Intervention: FRSW117
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.
Intervention: ADVATE
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.
Intervention: FRSW117
Outcomes
Primary Outcomes
Arm1 - T½ from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
Time Frame: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
Time required for the activity of the drug to reach half of its original value for participants.
Cmax from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
Time Frame: Pre-dose to 216 hours after the end of the infusion for Arm1; Pre-dose to 288 hours after the end of the infusion for Arm2
Maximum plasma activity during a dosing interval for participants.
Arm1 - T½ from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
Time Frame: Pre-dose to 216 hours after the end of the infusion for Arm1; Pre-dose to 288 hours after the end of the infusion for Arm2
Time required for the activity of the drug to reach half of its original value for participants.
Arm1 - Cmax from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
Time Frame: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
Maximum plasma activity during a dosing interval for participants.
Arm1 - CL from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
Time Frame: Pre-dose to 216 hours after the end of the infusion for Arm1; Pre-dose to 288 hours after the end of the infusion for Arm2
Rate at which the body removes the drug, measured as the volume of the plasma cleared of drug per unit time per unit weight for participants.
Arm1 - MRT from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
Time Frame: Pre-dose to 216 hours after the end of the infusion for Arm1; Pre-dose to 288 hours after the end of the infusion for Arm2
The average time that a drug molecule is present in the systemic circulation for participants.
Arm1 - MRT from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
Time Frame: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
The average time that a drug molecule is present in the systemic circulation for participants.
Arm1 - Incremental recovery from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
Time Frame: Pre-dose to 216 hours after the end of the infusion forArm1; Pre-dose to 288 hours after the end of the infusion for Arm2
The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants.
Arm1 - Incremental recovery from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
Time Frame: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants.
Number of participants with treatment-emergent adverse events (TEAEs).
Time Frame: assessed up to four weeks after FRSW117 administration.
Adverse events in the study were classified and evaluated according to the National Cancer Institute's Common Terminology for Adverse Events (NCI CTCAE V5.0).
Arm1 - CL from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
Time Frame: Pre-dose to 72 hours after the end of the infusion for Arm1; Pre-dose to120 hours after the end of the infusion for Arm2
Rate at which the body removes the drug, measured as the volume of the plasma cleared of drug per unit time per unit weight for participants.
Secondary Outcomes
- Evaluation of the level of anti-PEG-rFⅧFc antibody production in participants(assessed up to four weeks after FRSW117 administration.)
- Evaluation of the level of anti-PEG antibody production in participants(assessed up to four weeks after FRSW117 administration.)
- Number of participants with inhibitor development.(assessed up to four weeks after FRSW117 administration.)