Study of Efficacy and Safety of FRSW107 in Pediatric Patients With Severe Hemophilia A

NCT ID: NCT06136507

Last Updated: 2024-06-20

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-12-25
• Study Completion Date: 2026-12-31

Brief Summary

This study was divided into four stages: screening period, main trial period, extension period and follow-up period.

In the main trial, both groups received FRSW107 prophylactic therapy. The recommended initial dose of prophylactic administration was 50 IU/kg, the dose range was 25 to 50 IU/kg, and the recommended frequency of administration was once every three days (Q3D). The dose range could be adjusted according to the patient's response. The main trial period was prophylaxis up to ≥50 exposure days (EDs) and ≥6 months.

The investigator may adjust the dose according to the clinical efficacy of the subjects (the occurrence of bleeding and its clinical manifestations) and the concentration of FⅧ valley according to the following principles.

If necessary, the investigator may adjust the dosing interval according to the clinical efficacy of the subject (the occurrence of bleeding and its clinical manifestations) and the concentration of FⅧ. Investigators are advised to inform sponsors or their research partners when adjusting doses and dosing intervals during prophylaxis.

After participants completed prophylaxis until ≥50EDs and ≥6 months, participants' willingness and investigator evaluation were used to decide whether to enter the extended trial. All subjects entering the extended phase continued with the original prophylactic regimen until 100EDs was dosed.

During the main trial period and the extended preventive treatment period, if the subjects have breakthrough bleeding events requiring treatment, hemostatic treatment of breakthrough bleeding with investigational drugs can be performed. The researchers can refer to the treatment guidance for different degrees of bleeding in Table 6-1. Taking into account the subject's prophylactic dose, severity of bleeding, site and extent of bleeding, clinical status, and previous PK results (if any), the investigator determines the appropriate dose to administer (recommended dose range: 25 to 50 IU/kg) and dosing times until the investigator assessed significant control of bleeding episodes (e.g. reduction of pain and swelling) or return to pre-bleeding activity. If the bleeding episode stops, the subject will continue with the same dose and frequency of prophylactic medication as before the bleeding episode.

Conditions

Severe Hemophilia A

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

The main test period and the extension period

Group 1:≥6 years old and \<12 years old; Group 2: \<6 years old pediatric patients Preventive treatment: 25\~50 is recommendedlU/kg, Q3D, can adjust the dose to 65 IU/kg based on the patient's response, and if necessary, the investigator can adjust the frequency of administration based on the clinical outcome of the subject (the occurrence of bleeding and its clinical manifestations) and the FVIII valley concentration.PK intensive blood collection will be performed for the PK subgroup at V1 (DO) and appropriate PK blood collection will be performed at other specified visit time points. After completion of ∠50EDs and 26 months of treatment, the original prophylactic regimen can be continued until 100EDs

Group Type: EXPERIMENTAL

FRSW107

Intervention Type: DRUG

experimental：Q3D.≥50EDs， Expansion phase：Q3D.100EDs

Interventions

FRSW107

experimental：Q3D.≥50EDs， Expansion phase：Q3D.100EDs

Intervention Type: DRUG

Other Intervention Names

Recombinant Human Coagulation Factor Ⅷ，Fc Fusion Protein for Injection

Eligibility Criteria

Inclusion Criteria

1. Children <12 years old, male;

2. Weight >10kg;

3. clinically confirmed patients with severe hemophilia A (defined as confirmation at the time of screening or previous medical records: coagulation factor VI activity <1%);

4. Treated patients, that is, those who had previously received EVI treatment and met the following criteria: <6 years old patients who had been treated with coagulation factor VI for >50 exposure days (EDs250), and < 26 years old patients who had been treated with coagulation factor VI for >150 exposure days(> 150);

5. Normal prothrombin time (PT) or International normalized ratio (INR) <1.3;

6. At least 6 months of treatment and detailed records of bleeding events before screening;

7. The subject's legally authorized representative (i.e. guardian) fully understands and knows about this study and signs the informed consent. Children with the ability to give informed consent (≥8 years old) should be informed and sign the informed consent voluntarily;

Exclusion Criteria

1. People who have been allergic to any component of EVI preparation (including but not limited to mouse or hamster protein or virus vaccine, gene recombination preparation containing mouse or hamster protein, etc.); Those who have had serious adverse reactions to previous vaccine injections or have not recovered from mild to moderate adverse reactions to vaccine injections; 2.Patients with hypersensitivity or anaphylaxis after injection of coagulation factor VI or Fc fusion protein products; 3. Positive factor VI inhibitor at screening (20.6 BU/mL), or previous history of factor VI inhibitor, or family history of inhibitor; 4.the screening results of von Willebrand factor (vWE) antigen were lower than the lower limit of normal value; 5. Severe anemia (hemoglobin <60g/L) at the time of screening; 6. Platelet count <100×10⁹ during screening /L; 7.abnormal liver function: alanine aminotransferase (ALT), or aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN); Serum bilirubin (TBIL>3× ULN; 8. Patients with abnormal renal function: serum creatinine (SCr) >1.5×ULN or according toCreatinine clearance calculated by Cockcroft-Gault formula &lt; 60 mL/min (CTCAE Level 1); 9. hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody, anti-human immunodeficiency virus antibody (Anti-HIV) and anti-treponema pallidum specific antibody (Anti-TP) test has one or more positive; 10. Patients with coagulation dysfunction other than hemophilia A; 11,.have other medical conditions that may increase the risk of bleeding or blood clots; 12. Have a known mental disorder that may affect trial compliance; 13. Patients who have used EV preparations of any standard half-life (e.g., Bekochi, Koyuki, Biinstop, Renjie, etc.) within 3 days or 5 half-lives prior to the first dose; Patients who have used any other half-life extension FVI preparations within 4 days or 5 half-lives prior to dosing (older at the time of retrieval); 14. Patients who have used emesezumab within 6 months prior to first dosing; 15. Severe cardiovascular and cerebrovascular disease, such as cerebral arteritis, moyamoya disease, stroke, viral myocarditis, endocarditis, endocardial fibroplasia, severe arrhythmia, congestive heart failure (New York Heart Association grade > III), uncontrolled hypertension, thromboembolic disease, and uncontrolled diabetes, occurred within 6 months prior to the first medication; 16. Patients who had used monoclonal antibody therapy, Fc fusion protein products, or intravenous immunoglobulin within 3 months before the first dose; 17.those who underwent major surgical procedures and transfusions of blood or blood components within 4 weeks prior to initial dosing, or who plan to undergo elective surgery (other than minor surgery such as tooth extraction) during the study treatment period; Those who underwent major surgical procedures and transfusions of blood or blood components within 4 weeks prior to initial dosing, or who plan to undergo elective surgery during the study treatment period; 18.patients with fever, active infection, allergies (such as allergic rhinitis, allergic asthma, allergic dermatitis, etc.) within 2 weeks prior to the first dose； 19.people with immune deficiency diseases or autoimmune diseases such as systemic lupus erythematosus, or have a history of organ transplantation or stem cell transplantation; Systemic immunomodulators (such as corticosteroids (>10mg/ day equivalent dose of prednisone), alpha-interferon, immunoglobulin, cyclophosphamide, cyclosporin, etc.) used within 14 days prior to the first administration or planned during the study period were allowed to use inhaled, nasal, ocular, intraarticular or topical corticosteroids; 20.patients who were treated with any anticoagulation (other than heparin sealing treatment) or platelet aggregation inhibitors within 7 days prior to initial administration or who required anticoagulation (other than heparin sealing treatment) or platelet aggregation inhibitors during study therapy; 21. Participants who have participated in other clinical trials within 1 month before screening; 22.had other serious medical conditions from which the researchers did not believe they could benefit; He suffered from severe skin disease, which interfered with the observation of local injection reaction.

23. Subjects deemed unsuitable by other investigators.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 12 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu Gensciences lnc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Children's Hospital Affiliated to Chongqing Medical University

Chongqing, , China

Guangzhou Women and Children Medical Center

Guangzhou, , China

Nanfang Hospital, Southern Medical University

Guangzhou, , China

Affiliated Hospital of Guizhou Medical University

Guizhou, , China

Children's Hospital, Zhejiang University School of Medicine

Hangzhou, , China

Anhui Children's Hospital

Hefei, , China

The Second Affiliated Hospital of Anhui Medical University

Hefei, , China

Nanjing Children's Hospital

Nanjing, , China

Affiliated Hospital of Qingdao University

Qingdao, , China

Shenzhen Children's Hospital

Shenzhen, , China

Shanxi Children's Hospital

Taiyuan, , China

Beijing Children's Hospital Affiliated to Capital Medical University

Tianjing, , China

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, , China

Countries

China

Central Contacts

Lili Xu

Role: CONTACT

lilixu@gensciences.cn

+8618518760326

Facility Contacts

Jianwen Xiao

Role: primary

Hua Jiang

Role: primary

Xiaoqin Feng

Role: primary

Jiao Jin

Role: primary

Weiqun Xu

Role: primary

Tianping C, PhD

Role: primary

Ningling Wang

Role: primary

Yongjun Fang

Role: primary

Lirong Sun

Role: primary

Sixi Liu

Role: primary

Haiyan Lu

Role: primary

Runhui Wu, PhD

Role: primary

Qun Hu

Role: primary

Other Identifiers

SS-107-III03

Identifier Type: -

Identifier Source: org_study_id