a study to evaluate the pharmacokinetics，safety and tolerability of peg recombinant human coagulation factor viii-fc fusion protein for injection

Conditions: Severe Hemophilia A

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


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.

Keywords: severe hemophilia a peg recombinant human coagulation factor viii-fc fusion protein for injection pharmacokinetics efficacy and tolerability phase i