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

NCT03747653 | Unknown

• 1 other identifier: CTR20182090
• Study Type: observational
• Target: 12
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Hemophilia A

Keywords

Hemophilia A; Pharmacokinetics; Factor VIII-Fc Fusion Protein; Adolescent and Adult Patients; Phase I; Safety and Tolerability

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by CTCAE V5.0.

  Post dose of FRSW107 up to 28.

• Development of Inhibitor.

  Pre-dose and post dose of FRSW107 up to 28 days.

Study Arms (2)

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; Drug: FRSW107

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; Drug: FRSW107

Interventions

ADVATE DRUG

Patients will be administered a single dose of ADVATE.

Arm 1; Arm 2

FRSW107 DRUG

Patients will be administered a single dose of FRSW107 for Injection.

Arm 1; Arm 2

Eligibility Criteria

• Age: 12 Years - 60 Years
• Gender Eligibility Details: Hemophilia A is an X-chromosome-linked recessive inherited bleeding disorder caused by a deficiency of coagulation factor VIII (FVIII).
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Adolescent and Adult patients with Hemophilia A from clinical registration.

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kaifeng Pharmaceutical (Group) Co., Ltd.: lead
• Beijing Furen Biomedical Research Institute Co., Ltd.: collaborator

Study Sites (5)

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350000, China

Location

Southern Medical University Nanfang Hospital

Guangzhou, Guangzhou, 510515, 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

Hematology Department, Beijing Children's Hospital, Capital Medical University

Beijing, 100045, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

whole blood

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII

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

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: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2018
• First Posted: November 20, 2018
• Study Start: March 8, 2019
• Primary Completion: May 31, 2020
• Study Completion: May 31, 2020
• Last Updated: May 8, 2020

Record last verified: 2020-05

Locations

CN (5)