A Study to Evaluate the Pharmacokinetics，Safety and Tolerability of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection

NCT04864743 | Completed Phase 1

• 1 other identifier: CTR20210830
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 4

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

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

Outcome Measures

Primary Outcomes (11)

• 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

• 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.

Secondary Outcomes (3)

• 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.

Study Arms (2)

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.

Drug: ADVATE; Drug: FRSW117

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.

Drug: ADVATE; Drug: FRSW117

Interventions

ADVATE DRUG

a single dose.

Arm 1-ADVATE+FRSW117(25 IU/kg); Arm 2-ADVATE+FRSW117( 50 IU/kg)

FRSW117 DRUG

a single dose.

Also known as: PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection

Arm 1-ADVATE+FRSW117(25 IU/kg); Arm 2-ADVATE+FRSW117( 50 IU/kg)

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu Gensciences lnc.: lead

Study Sites (4)

Nanfang Hospital of Southern Medical University

Guangzhou, Guangzhou, 510515, China

Location

People's Hospital of Zhengzhou

Zhengzhou, Henan, 450053, China

Location

Jinan central hospital

Jinan, Shandong, 250013, China

Location

Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College.

Tianjin, Tianjin Municipality, 300020, China

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII; Injections

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Renchi Yang, PhD

  Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2021
• First Posted: April 29, 2021
• Study Start: June 22, 2021
• Primary Completion: October 17, 2021
• Study Completion: October 17, 2021
• Last Updated: September 8, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)