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.

NCT04456387 | Completed Phase 3

• 1 other identifier: CTR20201212
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 17

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.

Conditions

Hemophilia A

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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.

• 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.

• 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 Outcomes (16)

• Part A-rFVIIIFc incremental recovery (IR).

  For the duration of study participation, 6 months.

• Part A -Total Dose Required for Resolution of a Bleeding Episode.

  For the duration of study participation, 6 months.

• Part A -Number of injections required to resolve a bleeding episode.

  For the duration of study participation, 6 months.

• Part A -Quality of life assessment.

  For the duration of study participation, 6 months.

• Part B -Number of injections required to resolve a bleeding episode.

  For the duration of study participation, 6 months.

Other Outcomes (2)

• Part B-Response to treatment of bleeds.

  the duration of study participation, 6 months.

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events. (SAEs) as a Measure of Safety and Tolerability

  the duration of study participation, 6 months.

Study Arms (2)

Arm 1-on demand treatment

EXPERIMENTAL

Part A-Participants will receive on-demand treatment with Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection for 6 months.

Drug: Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection

Arm 2- prophylaxis treatment

EXPERIMENTAL

Part B-Participants will receive prophylaxis treatment with Recombinant Human Coagulation Factor VIII-Fc fusion for 6 months. 12 Participants of them will receive PK assessment 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.)，measured by one-stage assay, they would not be given prophylaxis treatment until the completion of PK blood collection.

Drug: Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection

Interventions

Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection DRUG

Participants received on-demand treatment, doses range from 30 IU/kg to 50 IU/kg, or doses divided on the discretion of the Investigator.

Arm 1-on demand treatment

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)

You may qualify if:

• )Male, aged 12 to 60 years
• )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.
• \) 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.
• \) Non-immune deficiency, with a certain immune capacity (CD4 \> 200/μL)
• \) Platelet count \> 100,000 platelets/μL.
• \) Normal prothrombin time or INR \< 1.3.
• \) Normal previous results of vWF antigen examination.
• \) Negative lupus anticoagulant.
• \) 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).
• \) 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 II immunoglobulin administration.
• \) Other coagulation disorder(s) in addition to hemophilia A.
• \) 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 \> 176.8µmol/L).
• \) 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 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 1 month prior screening.
• \) 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.
• \) 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

• Zhengzhou Gensciences Inc: lead

Study Sites (17)

Anhui Provincial Hospital

Hefei, Anhui, 230001, China

Location

Capital Medical University affiliated Beijing Children's Hospital

Beijing, Beijing Municipality, 100045, China

Location

Chongqing Three Gorges Central Hospital

Chongqing, Chongqing Municipality, 404000, China

Location

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

Location

The First Hospital of Lanzhou University

Lanzhou, Gansu, 730000, China

Location

The Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510260, China

Location

Nanfang Hospital of Southern Medical University

Guangzhou, Guangzhou, 510515, China

Location

The Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, 550004, China

Location

Henan provincial People's Hospital

Zhengzhou, He'nan, 450003, China

Location

Henan Cancer Hospital

Zhengzhou, He'nan, 450008, China

Location

Xiangya Hospital of Central South University

Changsha, Hunan, 410013, China

Location

The Affiliated Hospital of Xuzhou Medical College

Xuzhou, Jiangsu, 221000, China

Location

Jiangxi Provincial People's Hospital

Nanchang, Jiangxi, 330006, China

Location

Jinan central hospital

Ji'nan, Shandong, 250013, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, 266000, China

Location

The Second Hospital of Shanxi Medical University

Taiyuan, Shanxi, 030001, China

Location

Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

Tianjin, Tianjin Municipality, 300020, China

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

Injections

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)

Drug Administration Routes; Drug Therapy; Therapeutics

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: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2020
• First Posted: July 2, 2020
• Study Start: October 15, 2020
• Primary Completion: September 30, 2021
• Study Completion: September 30, 2021
• Last Updated: December 13, 2023

Record last verified: 2020-10

Locations

CN (17)