Clinical trial NCT04864743: A Study to Evaluate the Pharmacokinetics，Safety and Tolerability of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Severe Hemophilia A
Keywords: severe Hemophilia A
PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection
Pharmacokinetics
Efficacy and tolerability
Phase I
Lead sponsor: Jiangsu Gensciences lnc.
Sponsor class: INDUSTRY
First posted: 2021-04-29
Enrollment: 13
Sex: MALE
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Cmax from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
timeFrame: 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
measure: Arm1 - T½ from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
timeFrame: 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
measure: Arm1 - CL from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
timeFrame: 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
measure: Arm1 - MRT from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
timeFrame: 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
measure: Arm1 - Incremental recovery from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay.
timeFrame: 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: Arm1 - Cmax from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
timeFrame: 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
measure: Arm1 - T½ from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
timeFrame: 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
measure: Arm1 - CL from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
timeFrame: 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
measure: Arm1 - MRT from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
timeFrame: 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
measure: Arm1 - Incremental recovery from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay.
timeFrame: 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
measure: Number of participants with treatment-emergent adverse events (TEAEs).
timeFrame: assessed up to four weeks after FRSW117 administration.
Secondary outcomes:
measure: Evaluation of the level of anti-PEG-rFⅧFc antibody production in participants
timeFrame: assessed up to four weeks after FRSW117 administration.
measure: Evaluation of the level of anti-PEG antibody production in participants
timeFrame: assessed up to four weeks after FRSW117 administration.
measure: Number of participants with inhibitor development.
timeFrame: assessed up to four weeks after FRSW117 administration.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangzhou
city: Zhengzhou
country: China
facility: People's Hospital of Zhengzhou
state: Henan
city: Jinan
country: China
facility: Jinan central hospital
state: Shandong
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College.
state: Tianjin
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College.
name: Renchi Yang, PhD
role: PRINCIPAL_INVESTIGATOR
References: