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Study of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein (FRSW107) as Prophylactic Treatment.

2 septembre 2026 mis à jour par: Hangzhou Gensciences Biopharmaceutical Co., Ltd.

A Single-Arm, Open-Label, Multicenter Phase III Clinical Study Evaluating the Efficacy, Safety, Immunogenicity and Pharmacokinetics of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein (FRSW107) as Prophylactic Therapy in Patients With Severe Hemophilia A (Adults and Adolescents)

The indication for this product is to control and prophylaxis in patients with Hemophilia A (congenital Factor VIII deficiency):

The Primary Objective： To evaluate the efficacy of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) for prophylactic treatment in previously treated patients with severe Hemophilia A.

Secondary Objectives： To evaluate the health-related quality of life, pharmacokinetic (PK) profiles, safety and immunogenicity of Recombinant Human Coagulation Factor VIII-Fc Fusion Protein for Injection (FRSW107) for prophylactic treatment in previously treated subjects with severe Hemophilia A.

Aperçu de l'étude

Statut

Actif, ne recrute pas

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Estimé)

60

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Chine
      • Fuyang, Chine
        • Fuyang Hospital, Affiliated to Anhui Medical University
      • Fuzhou, Chine
        • Fujian Medical University Union Hospital
      • Guangzhou, Chine
        • Nanfang Hospital of Southern Medical University
      • Hefei, Chine
        • Anhui Provincial Hospital
      • Jinan, Chine
        • Jinan Central Hospital
      • Kunming, Chine
        • The Second Affiliated Hospital of Kunming Medical University
      • Nanning, Chine
        • The First Affiliated Hospital of Guangxi Medical University
      • Nantong, Chine
        • Affiliated Hospital of Nantong University
      • Nanyang, Chine
        • The First Affiliated Hospital of Nanyang Medical College
      • Qinghai, Chine
        • Qinghai Provincial People's Hospital
      • Taiyuan, Chine
        • The Second Hospital of Shanxi Medical University
      • Tangshan, Chine
        • North China University of Science and Technology Affiliated Hospital
      • Wenzhou, Chine
        • Wenzhou People's Hospital
      • Wuhan, Chine
        • Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology.
      • Wuxi, Chine
        • Affiliated Hospital of Jiangnan University
      • Xi'an, Chine
        • Xi'an Central Hospital
      • Zhengzhou, Chine
        • Henan Cancer Hospital
      • Zhengzhou, Chine
        • Zhengzhou People's Hospital
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, Chine
        • Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Enfant
  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

Inclusion Criteria:

1.12≤ age ≤65 year-old men; 2.Subjects with clinically confirmed severe hemophilia A, i.e. at screening (central laboratory testing) or previous medical records confirm: FⅧ activity < 1%; 3.Previous documented treatment with any recombinant and/or blood-derived coagulation factor Ⅷ products or cryoprecipitation products and dosed ≥150 exposure days (EDs≥150) ; 4.Normal prothrombin time (PT) or International Normalized Ratio (INR)<1.3; 5.Bleeding events were recorded in detail for at least 6 months prior to screening; 6.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

Exclusion Criteria:

  1. Known or suspected allergy to the investigational drug or its excipients, including mouse or hamster proteins;
  2. Hypersensitivity or anaphylaxis after FⅧ or IgG2 injection in the past;
  3. 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;
  4. Von Willebrand factor (vWF) antigen test results were lower than the lower limit of normal value;
  5. Severe anemia at the screening stage (hemoglobin < 60 g/L);
  6. Platelet count during screening period < 100×109 /L;
  7. 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;
  8. Subjects with abnormal renal function: Creatinine clearance (Ccr) <50 ml/min (according to Cockcroft and Gault formula); or Serum creatinine (Cr) >1.5x ULN;
  9. Subjects 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);
  10. Subjects with coagulation dysfunction other than hemophilia A;
  11. Have a medical condition that may increase the risk of bleeding;
  12. A history of drug or alcohol abuse;
  13. Have a known mental disorder that may affect trial compliance;
  14. Subjects who have received transfusions of blood or blood components within 4 weeks prior to screening;
  15. Participants who had participated in other Interventional clinical trials within 1 month before screening;
  16. Use of any anticoagulant or antiplatelet drugs, off-label maximum dose of non-steroidal anti-inflammatory drugs (NSAID) within 7 days prior to screening; Or subjects who need to be treated with anticoagulant or antiplatelet drugs or off-label maximum doses of SAID during clinical trials;
  17. Severe cardiovascular and cerebrovascular disease or major thromboembolic events, such as stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association [NYHA] grade ≥ III), and severe arrhythmias (including QTc interphase > 480 ms, corrected by Fridericia formula), uncontrolled hypertension (systolic ≥ 160 mmHg or diastolic ≥100 mmHg), deep vein thrombosis, etc.
  18. Subjects who have received emicizumab within 6 months prior to the first administration of study drug, or have previously received fitusiran (siRNA, brand name: CEPHEIN®) or gene therapy;
  19. Subjects who have received monoclonal antibody therapy, Fc fusion protein products, or intravenous immunoglobulin within 3 months prior to the first administration of study drug;
  20. Subjects who have undergone major surgery within 3 months prior to the first administration of study drug, or those who plan to receive surgery during the study period;
  21. Subjects who have received any standard half-life FⅧ preparations (e.g., Advate, Kovaltry, Octate, Recombinate, NovoEight, Anjiyin, etc.) within 3 days or 5 half-lives (whichever is longer) prior to the first administration of study drug; patients who have received any other extended half-life FⅧ preparations (e.g., Noxyte) within 4 days or 5 half-lives (whichever is longer) prior to the first administration of study drug;
  22. Study patients with fever, severe active bacterial or viral infection, and allergies within 2 weeks before the first administration of the drug;
  23. Systemic immunomodulators (such as glucocorticoids [> 10 mg/ day equivalent dose of prednisone], alpha-interferon, immunoglobulin, cyclophosphamide, cyclosporin, etc.) used within 14 days prior to the first administration of the study drug or planned during the study period were allowed to be inhaled, nasal spray, or topical corticosteroids;
  24. Those who had been vaccinated within 4 weeks prior to initial administration of the study drug; Or who plan to be vaccinated during PK blood collection (only for subjects in the PK subgroup);
  25. Plan to have a child or sperm donation during the entire trial period and within 3 months after the last dose, or do not want to use effective physical contraception (such as condoms, diaphragms, Iuds, etc.);
  26. Have other serious medical conditions that the researchers said could not benefit from them
  27. Subjects deemed unsuitable by other investigators.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: prophylactic treatment

Subjects in PK Subgroup receive a single and multiple dose of 50 IU/kg FRSW107 at Visit 1 and Visit 5, respectively. PK samples will be collected up to 72 hours after the start of administration.After completion of PK blood sampling for the first dose and prior to availability of the corresponding PK data, subjects may continue prophylactic treatment with FRSW107 at a dose of 50 IU/kg every 3 days until their PK data are obtained.Once the first-dose PK data of a subject are available, individualized prophylactic treatment with FRSW107 will be implemented based on the PK results. On the premise of maintaining a trough FVIII activity level of ≥1%, the investigator will determine the appropriate individualized prophylactic regimen for the subject. The recommended prophylactic dosing interval is Q3D, with an optional dose range of 25-50 IU/kg.

For subjects in the non-PK subgroup, the investigator will select the initial prophylactic dose within the recommended range of 25-50 IU/kg.
Médicament: FRSW107

For subjects in the PK subgroup: they will receive a dose of 50 IU/kg at the first dose visit 1 to obtain preliminary pharmacokinetic (PK) data. After assessment by the investigator, individualized prophylactic treatment (25~50 IU/kg, Q3D) will be administered to maintain the trough concentration of FVIII activity at ≥1%.

For subjects not in the PK subgroup: they will receive prophylactic treatment at a dose of 25~50 IU/kg once every three days.

If a subject experiences a breakthrough bleeding episode requiring treatment, the investigator shall determine the appropriate dosage (recommended dose range: 20~50 IU/kg) and administration frequency.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
ABR
Délai: 6 months
Annual rate of bleeding (ABR) during preventive treatment = Number of bleeding episode during the efficacy evaluation period/(number of treatment days /365.25)
6 months

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Safety Evaluation
Délai: 6 months
Incidence of positive FⅧ inhibitor (key secondary endpoint)
6 months
Immunogenicity Evaluation
Délai: 6 months
Incidence of positive anti-FRSW107 antibodies and anti-CHO antibodies; for subjects with positive anti-FRSW107 antibodies, additional testing for anti-rhFVIII antibodies shall be performed to assess their positive incidence.
6 months
Peak activity (Cmax)
Délai: At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).

Applicable to PK Subgroup:

  1. Single administration: Peak activity (Cmax).
  2. Multiple administrations: Cmax.
At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
Effective rate of hemostatic treatment
Délai: 6 months
During the prophylactic treatment period, breakthrough hemostatic therapy was evaluated based on a four-level scoring scale (excellent, good, moderate, ineffective), with scores of "excellent" or "good" indicating efficacy.
6 months
Annualized rate of spontaneous bleeds and annualized rate of traumatic bleeds.
Délai: 6 months
Annualized rate of spontaneous bleeds and annualized rate of traumatic bleeds.
6 months
Annualized Joint Bleed Rate (AJBR)
Délai: 6 months

Annualized Joint Bleed Rate (AJBR), including overall AJBR, annualized rate of spontaneous joint bleeds and annualized rate of traumatic joint bleeds.

AJBR = Number of joint bleeds during efficacy evaluation period / (Number of treatment days / 365.25).
6 months
Number of target joints.
Délai: 6 months
Number of target joints. Target joint definition: A joint with ≥3 spontaneous bleeds within any consecutive 6 months is defined as a target joint; a joint will no longer be classified as a target joint if it experiences ≤2 bleeds within any consecutive 12 months.
6 months
Dosing parameters of prophylactic treatment
Délai: 6 months
Dosing parameters of prophylactic treatment: total cumulative dose during study, annual total dose, mean dose per prophylactic administration; administration frequency: total number of injections, mean annual injection frequency; dosing interval: mean interval between prophylactic administrations throughout the prophylaxis period.
6 months
Factor VIII incremental recovery and trough levels during prophylactic treatment.
Délai: 6 months
Factor VIII incremental recovery and trough levels during prophylactic treatment.
6 months
Time interval between each bleeding episode and the prior prophylactic dose during prophylaxis.
Délai: 6 months
Time interval between each bleeding episode and the prior prophylactic dose during prophylaxis.
6 months
Dosing parameters for rescue hemostatic treatment of breakthrough bleeds during prophylaxis
Délai: 6 months
Dosing parameters for rescue hemostatic treatment of breakthrough bleeds during prophylaxis: mean dose, total cumulative dose and total number of administrations.
6 months
Hemophilia Joint Health Score version 2.1 (HJHS 2.1)
Délai: 6 months
Hemophilia Joint Health Score version 2.1 (HJHS 2.1): total HJHS 2.1 score, individual domain subscores, and their respective changes from baseline.
6 months
EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) and EuroQol Visual Analogue Scale (EQ VAS) .
Délai: 6 months
EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) and EuroQol Visual Analogue Scale (EQ VAS), together with their changes from baseline.The total healthy utility index score ranges of EQ-5D-5L from a minimum value of 0 points to a maximum value of 1 points,higher scores mean a better outcome.The total score ranges of EuroQol Visual Analogue Scale (EQ VAS) from a minimum value of 0 points to a maximum value of 100 points,higher scores mean a better outcome.
6 months
Incidence of insufficient therapeutic response
Délai: 6 months
Incidence of insufficient therapeutic response.
6 months
time to peak (Tmax)
Délai: At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).

Applicable to PK Subgroup:

  1. Single administration: time to peak (Tmax).
  2. Multiple administrations: Tmax.
At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
area under the concentration-time curve from time zero to the last quantifiable time point (AUC₀-ₗₐₛₜ)
Délai: At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).

Applicable to PK Subgroup:

  1. Single administration: area under the concentration-time curve from time zero to the last quantifiable time point (AUC₀-ₗₐₛₜ).
  2. Multiple administrations: AUC₀-ₗₐₛₜ.
At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
elimination half-life (t₁/₂)
Délai: At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
elimination half-life (t₁/₂)
At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
incremental recovery
Délai: At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
incremental recovery (calculated based on FⅧ Cmax measured after the end of infusion, unit: [IU/dL]/[IU/kg])
At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
The time for FⅧ activity to decline to 15%, 5%, 3% and 1% .
Délai: At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).
The time for FⅧ activity to decline to 15%, 5%, 3% and 1% respectively after study drug infusion.
At Visit 1 (Day 0 through Day 4) and Visit 5 (Day 160 through Day 164).

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Hangzhou Gensciences Biopharmaceutical Co., Ltd.

Les enquêteurs

  • Chaise d'étude: Renchi Yang, PhD, Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

12 juin 2026

Achèvement primaire (Estimé)

9 mars 2027

Achèvement de l'étude (Estimé)

21 juin 2027

Dates d'inscription aux études

Première soumission

16 juin 2026

Première soumission répondant aux critères de contrôle qualité

29 juin 2026

Première publication (Réel)

6 juillet 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

4 septembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

2 septembre 2026

Dernière vérification

1 juin 2026

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • SS-107-III04

Plan pour les données individuelles des participants (IPD)

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INDÉCIS

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

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