Phase 3 Clinical Project of Pegylated Recombinant Human Coagulation Factor VIII-Fc Fusion Protein

NCT06142552 | Recruiting Phase 3

• 1 other identifier: SS-117-III01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 28

Brief Summary

To evaluate the prophylactic efficacy of recombinant human coagulation factor Ⅷ-Fc fusion protein (FRSW117) for injection in patients with severe hemophilia A. To evaluate the safety of recombinant human coagulation factor Ⅷ-Fc fusion protein (FRSW117) for injection in patients with severe hemophilia A. Secondary purpose: To evaluate the efficacy of recombinant human coagulation factor Ⅷ-Fc fusion protein for injection (FRSW117) in hemostasis and surgical hemostasis in patients with severe hemophilia A. To evaluate the pharmacokinetic (PK) characteristics of recombinant human coagulation factor Ⅷ-Fc fusion protein (FRSW117) for injection in treated patients with severe hemophilia A. To evaluate the immunogenicity of recombinant human coagulation factor Ⅷ-Fc fusion protein (FRSW117) for injection in treated patients with severe hemophilia A.

Conditions

Severe Hemophilia A

Keywords

Pharmacokinetics; Safety; immunogenicity; effectiveness

Outcome Measures

Primary Outcomes (5)

• ABR

  Annual rate of bleeding (ABR) during preventive treatment = Number of bleeding during the efficacy evaluation period/(number of treatment days /365.25)

  1year

• Effective rate of bleeding treatment

  The hemostatic effect was evaluated according to a four-level scoring scale, including breakthrough bleeding treatment during preventive treatment and on-demand treatment during on-demand treatment

  2year

• Safety evaluation

  Incidence of positive FⅧ inhibitor. Adverse events/Adverse events: Adverse events during treatment (TEAE), serious Adverse events (SAEs), adverse events of particular concern (AESI), occurrences of adverse events that cause subjects to discontinue medication, drop out of the study, and death, and occurrences of the above metrics associated with the investigational drug. Injection site reaction. Laboratory tests: blood routine, urine routine, blood biochemistry, coagulation function, virology and immune function tests. Thrombosis markers. Vital signs, physical examination, neurological examination, 12-lead electrocardiogram, surgery-related complications. PEG level.

  3year

• Adverse events/reactions

  Adverse events during treatment (TEAE), serious Adverse events (SAEs), with a special focus on adverse events (AESI), adverse events that cause subjects to discontinue medication, drop out of the study, and die, etc.

  ALL

• Immunogenicity evaluation

  The positive rate of anti-FRSW117 antibody, anti-PEG antibody and anti-CHO antibody; When the anti-FRSW117 antibody was positive, the anti-RHFVIII antibody and anti-PEG antibody were further detected to evaluate the positive incidence

  ALL

Study Arms (3)

Prevention and Treatment Group (PPX group)

EXPERIMENTAL

Subjects received single and multiple doses of 50 IU/kg FRSW117 at first administration of V1 (D1), V4 (18w), and V7 (50w), and PK samples were collected until 168 h post-administration, respectively. During prophylaxis, FRSW117 is used for breakthrough therapy if the subject has a breakthrough bleeding event (i.e., a bleeding event during prophylaxis) that requires treatment.

Drug: FRSW117

On Demand/Preventive Treatment Group (On Demand /PPX Group)

EXPERIMENTAL

The appropriate dose and frequency of administration of FRSW117 is recommended until bleeding events are controlled or returned to pre-bleeding activity.

Drug: FRSW117

Perioperative management

EXPERIMENTAL

Patients in the PPX and on demand /PPX groups will be allowed to undergo surgery (both major and minor) during the main trial period (prior to 50w), while FRSW117 will be administered perioperatively

Drug: FRSW117

Interventions

FRSW117 DRUG

once a week, 50 weeks and as needed

Also known as: Recombinant human coagulation factor Ⅷ-Fc fusion protein for injection

On Demand/Preventive Treatment Group (On Demand /PPX Group); Perioperative management; Prevention and Treatment Group (PPX group)

Eligibility Criteria

• Age: 12 Years - 65 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• ≤ age ≤65 year-old men;
• Patients with clinically confirmed severe hemophilia A, i.e. at screening (central laboratory testing) or previous medical records confirm: FⅧ activity \< 1%；
• Previous documented treatment with any recombinant and/or blood-derived coagulation factor Ⅷ products or cryoprecipitation products and dosed ≥150 exposure days (EDs≥150)
• Normal prothrombin time (PT) or International Normalized Ratio (INR)\<1.3
• Bleeding events were recorded in detail for at least 6 months prior to screening（Participants in the on demand /PPX group were required to have at least 6 episodes of spontaneous bleeding within 6 months）
• Fully understand and know about this study and sign informed consent to participate in the clinical study voluntarily, subject and/or their guardian can cooperate with them for bleeding treatment at home, and have the ability to complete all study procedures

You may not qualify if:

• Known or suspected allergy to the investigational drug or its excipients, including mouse or hamster proteins;
• Hypersensitivity or anaphylaxis after FⅧ or IgG2 injection in the past;
• FⅧ inhibitor positive (≥0.6 BU/mL) during the screening period, or have a history of FⅧ inhibitor positive in the past, or a family history of FⅧ inhibitor positive;
• Von Willebrand factor (vWF) antigen test results were lower than the lower limit of normal value;
• Severe anemia at the screening stage (hemoglobin \&lt; 60 g/L);
• Platelet count during screening period \&lt; 100×109 /L;
• Abnormal liver function:
• Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) \>3 times upper limit of normal (ULN); or Serum total bilirubin (TBIL) \>1.5x ULN;
• Patients with abnormal renal function:
• Creatinine clearance (Ccr) \<50 ml/min (according to Cockcroft and Gault formula); orSerum creatinine (Cr) \>1.5x ULN;
• People with active hepatitis C, that is, hepatitis C virus (HCV) antibody positive and HCV RNA positive; Or anti-treponema pallidum specific antibody (TPHA) positive; Or positive for antibodies against the human immunodeficiency virus (HIV);
• Patients with coagulation dysfunction other than hemophilia A;
• Have a medical condition that may increase the risk of bleeding;
• A history of drug or alcohol abuse;
• Have a known mental disorder that may affect trial compliance;

Sponsors & Collaborators

• Jiangsu Gensciences lnc.: lead

Study Sites (28)

Beijing tongren hospital,CMU

Beijing, China

RECRUITING

XiangYa Hospital CentralSouth University

Changsha, China

RECRUITING

The Second Affiliated Hospital of Chongqing Medical University

Chongqing, China

NOT YET RECRUITING

Fujian Medical University Union Hospital

Fuzhou, China

RECRUITING

Nanfang Hospital of Southern Medical University

Guangzhou, China

RECRUITING

The First Affiliated Hospital，Zhejiang University School of Medicine

Hangzhou, China

NOT YET RECRUITING

Anhui Provincial Hospital

Hefei, China

RECRUITING

Jinan central hospital

Jinan, China

RECRUITING

The First Affiliated Hospital of Shandong First Medical University

Jinan, China

RECRUITING

The Second Affiliated Hospital of Kunming Medical University

Kunming, China

RECRUITING

The First Hospital of Lanzhou University

Lanzhou, China

RECRUITING

Jiangxi Provincial People's Hospital

Nanchang, China

RECRUITING

Nanjing Drum Tower Hospital

Nanjing, China

NOT YET RECRUITING

Affiliated Hospital of Nantong University

Nantong, China

RECRUITING

The Affiliated Hospital of Qingdao University

Qingdao, China

NOT YET RECRUITING

Ruijin Hospital, Shanghai Jiaotong University School Of Medicine

Shanghai, China

NOT YET RECRUITING

Shenzhen Second People's Hospital

Shenzhen, China

RECRUITING

The First Affiliated Hospital of Soochow University

Suzhou, China

RECRUITING

The Second Hospital of Shanxi Medical University

Taiyuan, China

RECRUITING

North China University of Science and Technology Affiliated Hospital

Tangshan, China

RECRUITING

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

Tianjin, China

RECRUITING

Affiliated Hospital of Jiangnan University

Wuxi, China

RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, China

RECRUITING

Zhenyu Li

Xuzhou, China

NOT YET RECRUITING

Subei People's Hospital of Jiangsu province

Yangzhou, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, China

RECRUITING

Henan Provincial People's Hospital

Zhengzhou, China

NOT YET RECRUITING

Zhengzhou People's Hospital

Zhengzhou, China

NOT YET RECRUITING

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

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

  STUDY CHAIR

Central Study Contacts

Chen Ling

CONTACT

+ 86 15896762713; chenling@gensciences.cn

Renchi Yang, PhD

CONTACT

Study Design

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

Study Record Dates

• First Submitted: November 7, 2023
• First Posted: November 21, 2023
• Study Start: December 27, 2023
• Primary Completion: January 15, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 28, 2024

Record last verified: 2024-02

Locations

CN (28)