Clinical trial NCT04456387: An Open Label Study to Determine the Safety and Efficacy of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection in Adolescent and Adult Patients With Hemophilia A.
Official title: An Open-Label, Multicenter Evaluation of the Safety and Efficacy of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) in Adolescent and Adult Patients With Hemophilia A.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A
Keywords: Hemophilia A
Efficacy and Safety
Factor VIII-Fc Fusion Protein
Adolescent and Adult Patients
Phase III
Pharmacokinetics
Lead sponsor: Zhengzhou Gensciences Inc
Sponsor class: INDUSTRY
First posted: 2020-07-02
Enrollment: 119
Sex: MALE
Minimum age (years): 12
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of the study are to evaluate the efficacy of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) in the Prevention and Treatment of Bleeding in patients with hemophilia A.

The secondary objectives are to evaluate the efficacy and safety of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) in the prevention and treatment of bleeding episodes, to investigate the quality of life in patients who used the FRSW107.


Eligibility criteria: Inclusion Criteria:

* 1)Male, aged 12 to 60 years
* 2)Severe hemophilia A. The activity of the coagulation factor VIII (FVIII:C) \< 1%, and previously treated with FVIII concentrate (s) for a minimum of 150 exposure days (EDs) prior to study entry.
* 3) No history of a positive inhibitor test (\< 0.6 BU) or clinical signs of decreased response to FVIII administrations within 2 years before the test or during the screening period. No Family history of inhibitors.
* 4) Non-immune deficiency, with a certain immune capacity (CD4 \> 200/μL)
* 5) Platelet count \> 100,000 platelets/μL.
* 6) Normal prothrombin time or INR \< 1.3.
* 7) Normal previous results of vWF antigen examination.
* 8) Negative lupus anticoagulant.
* 9) the patient has a detailed record of bleeding events for at least 6 months (the subject can be admitted to the on-demand treatment group with spontaneous bleeding ≥3 times within 6 months).
* 10) Capable of understanding and willing to comply with the conditions of the protocol have read (patient and/or guardian).

Exclusion Criteria:

* 1) Hypersensitive to any of the excipients of the test materials (e.g. allergic to murine or hamster origin heterologous proteins).
* 2) History of hypersensitivity or anaphylaxis associated with any FVIII or II immunoglobulin administration.
* 3) Other coagulation disorder(s) in addition to hemophilia A.
* 4) Patients with severe heart disease, including myocardial infarction, heart failure (III or higher level).
* 5) Clinically significant of other systematic diseases: alcoholism, drug abuse, mental disorders and mental retardation.
* 6) Significant hepatic or renal impairment (ALT and AST \> 2×ULN; serum bilirubin level \> 3 × upper limit of normal (ULN), BUN \> 2×ULN, Cr \> 176.8µmol/L).
* 7) 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.
* 8) 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.
* 9) Patients who previously participated in the other clinical trials within 1 month prior screening.
* 10) 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.
* 11) Any life-threatening disease or condition which, according to the investigator's judgment, could not benefit from the trial participation.
* 12) Patient who is considered by the other investigators not suitable for clinical study.

NOTE:Other protocol-defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Part A - score of bleeding symptoms and Vital signs.
timeFrame: For the duration of study participation, 6 months.
measure: Part B- Annualized Bleeding Rates(ABR).
timeFrame: For the duration of study participation, 6 months.
measure: Part B-Number of target joints.
timeFrame: For the duration of study participation, 6 months.
Secondary outcomes:
measure: Part A-rFVIIIFc incremental recovery (IR).
timeFrame: For the duration of study participation, 6 months.
measure: Part A -Total Dose Required for Resolution of a Bleeding Episode.
timeFrame: For the duration of study participation, 6 months.
measure: Part A -Number of injections required to resolve a bleeding episode.
timeFrame: For the duration of study participation, 6 months.
measure: Part A -Quality of life assessment.
timeFrame: For the duration of study participation, 6 months.
measure: Part B -Number of injections required to resolve a bleeding episode.
timeFrame: For the duration of study participation, 6 months.
measure: Part B -Quality of life assessment.
timeFrame: For the duration of study participation, 6 months.
measure: Part B -Number of participants with inhibitor development
timeFrame: 6 months and at least 50 exposure days.
measure: Part B - Number of Participants With Incidence of Antibody Formation to CHINESE HAMSTER OVARY (CHO).
timeFrame: before and the duration of study participation, 6 months.
measure: Part B -Number of All Bleeds.
timeFrame: before and the duration of study participation, 6 months.
measure: Part B-Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay
timeFrame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
measure: Part B-Half-life (t½) as Measured by aPTT Clotting Assay
timeFrame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
measure: Part B-Clearance (CL) as Measured by the aPTT Clotting Assay
timeFrame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
measure: Part B-Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay.
timeFrame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
measure: Part B-Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay.
timeFrame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
measure: Part B-Time of Cmax (Tmax) as Measured by aPTT Clotting Assay.
timeFrame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
measure: Part B-Area Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay.
timeFrame: Samples taken at pre-injection, and post dose up to 96 hours at ED1 and ED35(Participants will be tested for PK assessment at timepoints throughout the study based on exposure days (ED). One ED is equivalent to a 24 hours period in which drug is dosed.).
Other outcomes:
measure: Part B-Response to treatment of bleeds.
timeFrame: the duration of study participation, 6 months.
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events. (SAEs) as a Measure of Safety and Tolerability
timeFrame: the duration of study participation, 6 months.
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Capital Medical University affiliated Beijing Children's Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Three Gorges Central Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangzhou
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Zhengzhou
country: China
facility: Henan provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical College
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Ji'nan
country: China
facility: Jinan central hospital
state: Shandong
city: QingDao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi Medical University
state: Shanxi
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
state: Tianjin
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
name: Renchi Yang, PhD
role: PRINCIPAL_INVESTIGATOR
References: