Severe Hemophilia A
Conditions
Keywords
severe Hemophilia A, PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection, Pharmacokinetics, Efficacy and tolerability, Phase I
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
Sponsors
Jiangsu Gensciences lnc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-emergent adverse events (TEAEs). | 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. | 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. |
| Arm1 - MRT from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay. | 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 ADVATE Measured by One-Stage Clotting Assay. | 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. |
| Cmax from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. | 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. | 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 - CL from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. | 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. | 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 - Incremental recovery from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. | 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 - Cmax from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay. | 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 - T½ from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Number of participants who developed a positive FVIII inhibitor level (≥0.6 Bethesda unit \[BU\]) during the study was summarized and classified as participants developing low titer inhibitor (i.e. ≤ 5.0 BU) and participants developing high titer inhibitor (i.e. \> 5.0 BU). |
| Evaluation of the level of anti-PEG-rFⅧFc antibody production in participants | assessed up to four weeks after FRSW117 administration. | — |
Countries
China
Outcome results
None listed