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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1-ADVATE+FRSW117(25 IU/kg) | Experimental | 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. |
|
| Arm 2-ADVATE+FRSW117( 50 IU/kg) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ADVATE | Drug | a single dose. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cmax from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. | Maximum plasma activity during a dosing interval for participants. | 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 |
| Arm1 - T½ from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. | Time required for the activity of the drug to reach half of its original value for participants. | 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 |
| Arm1 - CL from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. | 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. | 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 |
| Arm1 - MRT from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. | The average time that a drug molecule is present in the systemic circulation for participants. | 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 |
| Arm1 - Incremental recovery from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. | The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Renchi Yang, PhD | Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nanfang Hospital of Southern Medical University | Guangzhou | Guangzhou | 510515 | China | ||
| People's Hospital of Zhengzhou |
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| FRSW117 | Drug | a single dose. |
|
|
| Arm1 - Cmax from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay. |
Maximum plasma activity during a dosing interval for participants. |
| 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 |
| Arm1 - T½ from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay. | Time required for the activity of the drug to reach half of its original value for participants. | 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 |
| Arm1 - CL from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay. | 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. | 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 |
| Arm1 - MRT from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay. | The average time that a drug molecule is present in the systemic circulation for participants. | 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 |
| Arm1 - Incremental recovery from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay. | The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants. | 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 |
| Number of participants with treatment-emergent adverse events (TEAEs). | 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). | assessed up to four weeks after FRSW117 administration. |
| Number of participants with inhibitor development. | 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). | assessed up to four weeks after FRSW117 administration. |
| Zhengzhou |
| Henan |
| 450053 |
| China |
| Jinan central hospital | Jinan | Shandong | 250013 | China |
| Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College. | Tianjin | Tianjin Municipality | 300020 | China |
| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| D005169 | Factor VIII |
| D007267 | Injections |
| ID | Term |
|---|---|
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011498 | Protein Precursors |
| D001685 | Biological Factors |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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