A Study of Repeat Dosing of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection

A Phase II, Multicentre, Open-label Study to Evaluate the Pharmacokinetic, Safety and Preliminary Efficacy of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection in Subjects With Severe Hemophilia A

Primary objective: To assess the pharmacokinetics, Safety and immunogenicity of Repeat Dosing of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection With Severe Hemophilia A(FRSW117) Secondary objectives: To assess Preliminary efficacy of Repeat Dosing of PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection With Severe Hemophilia A.

Study Overview

• Status: Completed
• Conditions: Severe Hemophilia A
• Intervention / Treatment: Drug: FRSW117

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450000
      • People's Hospital of Zhengzhou
  • Jiangsu
    • Wuxi, Jiangsu, China, 214100
      • Affiliated Hospital of Jiangnan University
  • Shandong
    • Qingdao, Shandong, China, 266000
      • The affiliated hospital of Qingdao university
    • Rizhao, Shandong, China, 276800
      • People's Hospital of Rizhao
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• The activity of the coagulation factor VIII (FVIII:C) < 1%.
• Patients previously treated with FVIII concentrate (s) for a minimum of 150 exposure days (EDs) prior to study entry
• Normal prothrombin time or INR < 1.3
• Negative lupus anticoagulant

Key Exclusion Criteria:

• Hypersensitive to any of the excipients of the test materials (e.g. allergic to murine or hamster origin heterologous proteins)
• History of hypersensitivity or anaphylaxis associated with any FVIII or II immunoglobulin administration
• Current FVIII inhibitor-positive or history of FVIII inhibitor-positive
• Other coagulation disorder(s) in addition to hemophilia A.• Significant hepatic or renal impairment (ALT and AST > 2×ULN; serum bilirubin level > 2 × upper limit of normal (ULN), Urea /BUN > 2×ULN, Cr > 176.8 µmol/L)
• One or more clinically significant tests for Human Immunodeficiency Virus (HIV), Antisyphilitic spirulina (TPHA) and Hepatitis C Virus (HCV) Antibody
• Patients who received any anticoagulant or antiplatelet therapy within one week prior screening or need to receive an anticoagulant or antiplatelet therapy during the period of clinical trials
• Patients having major surgery or receiving blood or bood 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 one 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

Other protocol-defined inclusion/exclusion Criteria May Apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 prophylaxis treatment; Subjects of high dose group are being received four doses of FRSW117. dosing on day1(ED1), day8(ED2), day15(ED3), day22(ED4) respectively. Subjects of low dose group are being received four doses of FRSW117. dosing on day1(ED1), day8(ED2), day15(ED3), day22(ED4) respectively. All subjects are being received PK assessment in ED1 and ED4.	Drug: FRSW117; Subjects of high dose group are being received four doses(50 IU/kg,once a week or every 7 days) of FRSW117. Subjects of low dose group (40 IU/kg,once a week or every 7 days)are being received four doses of FRSW117.; Other Names: PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum measured concentration of FVIII:C (Cmax)	Measured by One-Stage Clotting Assay	Pre-dose and post dose up to 10 days
Time required for the concentration of the drug to reach half of its original value (T1/2)	Measured by One-Stage Clotting Assay	Pre-dose and post dose up to 10 days
Area Under the Curve to Infinity (AUC)	Measured by One-Stage Clotting Assay	Pre-dose and post dose up to 10 days
The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time (CL)	Measured by One-Stage Clotting Assay	Pre-dose and post dose up to 10 days
Evaluation of the level of anti-PEG-rFⅧFc antibody production in participants		Pre-dose and post dose up to 36 days
Evaluation of the level of anti-PEG antibody production in participants		Pre-dose and post dose up to 36 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE V5.0	Adverse events related to PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein according to Common Terminology Criteria for Adverse Events (CTCAE) NCI.V5.0.	Pre-dose and post dose up to 36 days
Development of Inhibitor	Measured by the Nijmegen-Modified Bethesda Assay	Pre-dose and post dose up to 36 days
score of bleeding symptoms and Vital signs	Response to treatment with PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for bleeding episodes, using the 4-point bleeding response scale	Pre-dose and post dose up to 36 days

Collaborators and Investigators

• Sponsor: Jiangsu Gensciences lnc.
• Investigators: Principal Investigator: Renchi Yang, PhD, Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College.

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Actual): August 21, 2022
• Study Completion (Actual): August 21, 2022

Study Registration Dates

• First Submitted: February 22, 2022
• First Submitted That Met QC Criteria: February 22, 2022
• First Posted (Actual): March 3, 2022

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Preliminary efficacy; Pharmacokinetics;; Safety;; immunogenicity
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Coagulants; Factor VIII
• Other Study ID Numbers: CTR20220283

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No