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.

Hemophilia A Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04456387
• Other study ID #: CTR20201212
• Status: Completed
• Phase: Phase 3
• Start date: October 15, 2020
• Est. completion date: September 30, 2021

Study information

• Verified date: October 2020
• Source: Zhengzhou Gensciences Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: September 30, 2021
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Drug:
• Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection
Participants received on-demand treatment, doses range from 30 IU/kg to 50 IU/kg, or doses divided on the discretion of the Investigator.
• Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection
Participants received prophylaxis treatment at 50 IU/kg every three days.

Locations

Country	Name	City	State
China	Capital Medical University affiliated Beijing Children's Hospital	Beijing	Beijing
China	Xiangya Hospital of Central South University	Changsha	Hunan
China	Chongqing Three Gorges Central Hospital	Chongqing	Chongqing
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangzhou
China	The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	The Affiliated Hospital of Guizhou Medical University	Guiyang	Guizhou
China	Anhui Provincial Hospital	Hefei	Anhui
China	Jinan central hospital	Ji'nan	Shandong
China	The First Hospital of Lanzhou University	Lanzhou	Gansu
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	The Affiliated Hospital of Qingdao University	QingDao	Shandong
China	The Second Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College	Tianjin	Tianjin
China	The Affiliated Hospital of Xuzhou Medical College	Xuzhou	Jiangsu
China	Henan Cancer Hospital	Zhengzhou	Henan
China	Henan provincial People's Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Zhengzhou Gensciences Inc

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Part B-Response to treatment of bleeds.	Participants or caregivers were asked to assess the response to treatment of bleeds as excellent, good, moderate or poor. Percentage of bleeds per assessment was summarized and reported.	the duration of study participation, 6 months.
Other	Number of Participants With Adverse Events (AEs) and Serious Adverse Events. (SAEs) as a Measure of Safety and Tolerability	An AE is any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition.	the duration of study participation, 6 months.
Primary	Part A - score of bleeding symptoms and Vital signs.	Response to treatment with rFVIIIFc for bleeding episodes, using the 4-point bleeding response scale.	For the duration of study participation, 6 months.
Primary	Part B- Annualized Bleeding Rates(ABR).	Annualized bleeding rate = (number of bleeding episodes during the efficacy, period/total number of days during the efficacy period)*365.25. The efficacy period begins with the first prophylactic dose of FRSW107 and ends with the last dose (for prophylaxis or a bleed). Surgery/rehabilitation periods and PK evaluation periods are not included in the efficacy period. A bleeding episode started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, within which any symptoms of bleeding at the same location or injections less than or equal to 72 hours apart were considered the same bleeding episode. Any injection to treat the bleeding episode taken more than 72 hours after the preceding one was considered the first injection to treat a new bleeding episode at the same location. Any bleeding at a different location was considered a separate bleeding episode, regardless of time from last injection.	For the duration of study participation, 6 months.
Primary	Part B-Number of target joints.	The joint with =3 times of spontaneous bleeding in 6 consecutive months is the target joint, while the joint with < 2 times of bleeding in 12 consecutive months is no longer the target joint.	For the duration of study participation, 6 months.
Secondary	Part A-rFVIIIFc incremental recovery (IR).	Incremental recovery of Factor VIII (FVIII) within 1 hour after end of infusions was determined and mean recovery values were reported.	For the duration of study participation, 6 months.
Secondary	Part A -Total Dose Required for Resolution of a Bleeding Episode.	The total dose required to resolve a bleeding episode per participant, based on the efficacy period. The efficacy period begins with the first dose and ends with the last dose (for a bleed). For 'Per bleeding episode' values, for each bleeding episode, the total dose is the sum of the doses (IU/kg) administered across all injections given to treat that bleeding episode. For 'Per participant' values, the total dose (IU/kg) used to resolve each bleed is averaged across all bleeding episodes per participant.Quality of life assessment.	For the duration of study participation, 6 months.
Secondary	Part A -Number of injections required to resolve a bleeding episode.	The number of injections required to resolve a bleeding episode per participant, based on the efficacy period. The efficacy period begins with the first dose and ends with the last dose (for a bleed). All injections given from the initial sign of a bleed, until the last date/time within the bleed window are counted. The resolution of a bleed is defined as no sign of bleeding following injection for the bleed. For 'Per participant' values, the number of injections required to resolve each bleed is averaged across all bleeding episodes per participant.	For the duration of study participation, 6 months.
Secondary	Part A -Quality of life assessment.	Quality of life assessment by Haemophilia Joint Health Score(HJHS).	For the duration of study participation, 6 months.
Secondary	Part B -Number of injections required to resolve a bleeding episode.	The number of injections required to resolve a bleeding episode per participant, based on the efficacy period. The efficacy period begins with the first prophylactic dose and ends with the last dose (for prophylaxis or a bleed). All injections given from the initial sign of a bleed, until the last date/time within the bleed window are counted. The resolution of a bleed is defined as no sign of bleeding following injection for the bleed. For 'Per participant' values, the number of injections required to resolve each bleed is averaged across all bleeding episodes per participant.	For the duration of study participation, 6 months.
Secondary	Part B -Quality of life assessment.	Quality of life assessment by Haemophilia Joint Health Score(HJHS).	For the duration of study participation, 6 months.
Secondary	Part B -Number of participants with inhibitor development	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).	6 months and at least 50 exposure days.
Secondary	Part B - Number of Participants With Incidence of Antibody Formation to CHINESE HAMSTER OVARY (CHO).	A test to analyze the formation of antibodies to CHO.	before and the duration of study participation, 6 months.
Secondary	Part B -Number of All Bleeds.	The annualized number of bleeds experienced by participants.	before and the duration of study participation, 6 months.
Secondary	Part B-Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay	Maximum measured concentration of rFVIIIFc.	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.).
Secondary	Part B-Half-life (t½) as Measured by aPTT Clotting Assay	Time required for the concentration of the drug to reach half of its original value.	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.).
Secondary	Part B-Clearance (CL) as Measured by the aPTT Clotting Assay	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.	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.).
Secondary	Part B-Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay.	The apparent volume of distribution at steady state. (Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.).	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.).
Secondary	Part B-Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay.	The average time at which the number of absorbed molecules reside in the body, after single-dose administration.	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.).
Secondary	Part B-Time of Cmax (Tmax) as Measured by aPTT Clotting Assay.	Time at which maximum activity (Cmax) is observed.	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.).
Secondary	Part B-Area Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay.	Area under the plasma concentration time-curve from zero to the last measured concentration.	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.).