A Study to Evaluate the Pharmacokinetics of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection

A Phase I, Multicentre, Open-label, Self-control Study to Evaluate the Pharmacokinetics of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection in Adolescent and Adult Patients With Hemophilia A

Primary objective: To assess the pharmacokinetics of Recombinant Human Coagulation Factor VIII-Fc fusion protein for Injection at two dose levels in patients with hemophilia A.

Secondary objectives: To assess Safety and Tolerability by monitoring FVIII recovery and adverse events in patients with hemophilia A.

Study Overview

• Status: Unknown
• Conditions: Hemophilia A
• Intervention / Treatment: Drug: ADVATE; Drug: FRSW107

• Study Type: Observational
• Enrollment (Anticipated): 12

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100045
    • Hematology Department, Beijing Children's Hospital, Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Fujian Medical University Union Hospital
  • Guangzhou
    • Guangzhou, Guangzhou, China, 510515
      • Southern Medical University Nanfang Hospital
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
  • 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 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Adolescent and Adult patients with Hemophilia A from clinical registration.

Description

Inclusion Criteria:

• 12 years to 60 years, male.
• The activity of the coagulation factor VIII (FVIII:C) < 2%, and previously treated with FVIII concentrate (s) for a minimum of 150 exposure days (EDs) prior to study entry.
• Non-immune deficiency (CD4 > 200/μL).
• Non-acute hemorrhagic state.
• No history of a positive inhibitor test (< 0.6 BU) or clinical signs of decreased response to FVIII administrations. No Family history of inhibitors.
• Platelet count > 100,000 platelets/μL.
• Normal prothrombin time or INR < 1.3.
• Normal thrombin time (TT).
• Normal previous results of vWF antigen examination.
• Negative lupus anticoagulant .
• Capable of understanding and willing to comply with the conditions of the protocol have read (patient and/or guardian).

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 IgG2 administration.
• Current FVIII inhibitor-positive or history of FVIII inhibitor-positive.
• Other coagulation disorder(s) in addition to hemophilia A.
• Infusion of any products containing FVIII within 4 days prior screening or within 72 h prior to administration.
• Patients with severe heart disease, including myocardial infarction, heart failure (III or higher level).
• 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) , BUN > 2×ULN, Cr > 2.0 mg/dL).
• 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 1 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm 1; Participants will receive a single intravenous (i.v.) injection of ADVATE followed by a single intravenous (i.v.) injection of Recombinant Human Coagulation Factor VIII-Fc fusion protein for Injection (FRSW107) at a low dose.	Drug: ADVATE; Patients will be administered a single dose of ADVATE.; Drug: FRSW107; Patients will be administered a single dose of FRSW107 for Injection.
Arm 2; Participants will receive a single intravenous (i.v.) injection of ADVATE followed by a single intravenous (i.v.) injection of Recombinant Human Coagulation Factor VIII-Fc fusion protein for Injection (FRSW107) at a high dose.	Drug: ADVATE; Patients will be administered a single dose of ADVATE.; Drug: FRSW107; Patients will be administered a single dose of FRSW107 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 the One-stage aPTT Clotting Assay.	Pre-dose and post dose of FRSW107 up to 10 days.
Time required for the concentration of the drug to reach half of its original value (T1/2).	Measured by the One-stage aPTT Clotting Assay.	Pre-dose and post dose of FRSW107 up to 10 days.
Area Under the Curve to Infinity (AUC).	Measured by the One-stage aPTT Clotting Assay.	Pre-dose and post dose of FRSW107 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 the One-stage aPTT Clotting Assay.	Pre-dose and post dose of FRSW107 up to 10 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 Recombinant Human Coagulation Factor VIII-Fc fusion protein for Injection according to Common Terminology Criteria for Adverse Events (CTCAE) NCI.V5.0.	Post dose of FRSW107 up to 28.
Development of Inhibitor.	Measured by the Nijmegen-Modified Bethesda Assay.	Pre-dose and post dose of FRSW107 up to 28 days.

Collaborators and Investigators

• Sponsor: Kaifeng Pharmaceutical (Group) Co., Ltd.
• Collaborators: Beijing Furen Biomedical Research Institute Co., Ltd.
• 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): March 8, 2019
• Primary Completion (Anticipated): May 31, 2020
• Study Completion (Anticipated): May 31, 2020

Study Registration Dates

• First Submitted: November 12, 2018
• First Submitted That Met QC Criteria: November 17, 2018
• First Posted (Actual): November 20, 2018

Study Record Updates

• Last Update Posted (Actual): May 8, 2020
• Last Update Submitted That Met QC Criteria: May 7, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Phase I; Safety and Tolerability; Hemophilia A; Factor VIII-Fc Fusion Protein; Adolescent and Adult Patients
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: CTR20182090

Drug and device information, study documents

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