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

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ClinicalTrials.gov Identifier: NCT04864743
Recruitment Status : Recruiting
First Posted : April 29, 2021
Last Update Posted : July 14, 2021
Sponsor:
Information provided by (Responsible Party):
Jiangsu Gensciences lnc.

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


Condition or disease Intervention/treatment Phase
Severe Hemophilia A Drug: ADVATE Drug: FRSW117 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : June 22, 2021
Estimated Primary Completion Date : April 30, 2022
Estimated Study Completion Date : July 30, 2022


Arm Intervention/treatment
Experimental: Arm 1-ADVATE+FRSW117(25 IU/kg)
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
a single dose.

Drug: FRSW117
a single dose.
Other Name: PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection

Experimental: Arm 2-ADVATE+FRSW117( 50 IU/kg)
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
a single dose.

Drug: FRSW117
a single dose.
Other Name: PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection

Experimental: Arm 3-ADVATE+FRSW117(65 IU/kg)
Subjects received two treatments: 65 IU/kg ADVATE in the first period, followed by 65 IU/kg FRSW117 in the second period, with a washout period before each treatment.
Drug: ADVATE
a single dose.

Drug: FRSW117
a single dose.
Other Name: PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection




Primary Outcome Measures :
  1. Cmax from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. [ Time Frame: 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 and Arm3.. ]
    Maximum plasma activity during a dosing interval for participants.

  2. Arm1 - T½ from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. [ Time Frame: 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 and Arm3. ]
    Time required for the activity of the drug to reach half of its original value for participants.

  3. Arm1 - CL from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. [ Time Frame: 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 and Arm3. ]
    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.

  4. Arm1 - MRT from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. [ Time Frame: 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 and Arm3. ]
    The average time that a drug molecule is present in the systemic circulation for participants.

  5. Arm1 - Incremental recovery from time 0 to the last data point for FRSW117 Measured by One-Stage Clotting Assay. [ Time Frame: 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 and Arm3. ]
    The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants.

  6. Arm1 - Cmax from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay. [ Time Frame: 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 and Arm3. ]
    Maximum plasma activity during a dosing interval for participants.

  7. Arm1 - T½ from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay. [ Time Frame: 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 and Arm3. ]
    Time required for the activity of the drug to reach half of its original value for participants.

  8. Arm1 - CL from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay. [ Time Frame: 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 and Arm3. ]
    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.

  9. Arm1 - MRT from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay. [ Time Frame: 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 and Arm3. ]
    The average time that a drug molecule is present in the systemic circulation for participants.

  10. Arm1 - Incremental recovery from time 0 to the last data point for ADVATE Measured by One-Stage Clotting Assay. [ Time Frame: 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 and Arm3. ]
    The rise in FVIII activity in IU/dL per unit dose administered in IU/kg for participants.

  11. Number of participants with treatment-emergent adverse events (TEAEs). [ Time Frame: assessed up to four weeks after FRSW117 administration. ]
    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).


Secondary Outcome Measures :
  1. Evaluation of the level of anti-PEG-rFⅧFc antibody production in participants [ Time Frame: assessed up to four weeks after FRSW117 administration. ]
  2. Evaluation of the level of anti-PEG antibody production in participants [ Time Frame: assessed up to four weeks after FRSW117 administration. ]
  3. Number of participants with inhibitor development. [ Time Frame: assessed up to four weeks after FRSW117 administration. ]
    Number of participants who developed a positive FVIII inhibitor level (≥0.6 Bethesda unit [BU]) during the study was summarized and classified as participants developing low titer inhibitor (i.e. ≤ 5.0 BU) and participants developing high titer inhibitor (i.e. > 5.0 BU).



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Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04864743


Contacts
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Contact: Weichuan Mo +86-010-67806990 weichuanmo@gensciences.cn

Locations
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China, Guangzhou
Nanfang Hospital of Southern Medical University Recruiting
Guangzhou, Guangzhou, China, 510515
Contact: Jing Sun         
China, Henan
People's Hospital of Zhengzhou Recruiting
Zhengzhou, Henan, China, 450053
Contact: Shuxia Guo         
China, Shandong
Jinan central hospital Recruiting
Jinan, Shandong, China, 250013
Contact: Yun Chen         
Contact: Qing Wen         
China, Tianjin
Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College. Recruiting
Tianjin, Tianjin, China, 300020
Contact: Renchi Yang, PhD       rcyang65@163.com   
Sponsors and Collaborators
Jiangsu Gensciences lnc.
Investigators
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Principal Investigator: Renchi Yang, PhD Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College.
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Responsible Party: Jiangsu Gensciences lnc.
ClinicalTrials.gov Identifier: NCT04864743    
Other Study ID Numbers: CTR20210830
First Posted: April 29, 2021    Key Record Dates
Last Update Posted: July 14, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jiangsu Gensciences lnc.:
severe Hemophilia A
PEG Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection
Pharmacokinetics
Efficacy and tolerability
Phase I
Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants