Von Willebrand disease
Conditions
Interventions
Experimental group: This is a multiple-dose, randomized, open-label clinical trial to evaluate the efficacy, safety, and PK/PD characteristics of SR604 in patients with von Willebrand disease. The scr
Sponsors
The First Affiliated Hospital of Soochow University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. When signing the informed consent form, the age should be between 18 and 65 years old (inclusive), and gender is not restricted. 2. During the screening process, patients who can provide clear diagnostic evidence and have a definite diagnosis of von Willebrand Disease (VWD) with a clear VWD classification are eligible. 3. Within the 6 months prior to screening, the number of new bleeding events should be >= 4 times. 4. Before the first medication administration, there should be no active bleeding symptoms. 5. The subject or a fair witness should fully understand and be able to comply with the requirements of the trial protocol, have the willingness to complete the study as planned, and voluntarily cooperate with the provision of biological samples for testing. They should be able to understand the procedures and methods of this clinical trial, have given full informed consent, and the patient voluntarily participates and signs the informed consent form themselves.
Exclusion criteria
Exclusion criteria: 1. Patients with a history of hypersensitivity reaction to the test drug formulation or any of its components; 2. Those who are intolerant to subcutaneous injection or have other local skin abnormalities or skin diseases that affect the administration and safety assessment; 3. Those meeting one of the following criteria during the screening period: hemoglobin = 2.5 times the upper limit of normal (ULN), or total bilirubin >= 1.5 times ULN; or serum creatinine (Cr) >= 1.5 times ULN; anti-human immunodeficiency virus (HIV) antibody positive; 4. Those with any bleeding disorder other than von Willebrand disease (such as hemophilia A or B, congenital coagulation factor VII deficiency, acquired von Willebrand syndrome (AVWS), platelet-type von Willebrand disease, hereditary thrombocytopenia, etc.); or those with significantly abnormal coagulation indicators due to other diseases (such as platelet disorders, vitamin K deficiency, etc.); 5. Those with protein C deficiency or protein S deficiency; 6. Those who have a history of thrombosis before signing the informed consent or currently have a thrombosis family history, or have a history of thrombophilia; 7. Those who have experienced severe bleeding due to VWD such as intracranial hemorrhage, esophageal variceal bleeding, etc. within 2 years before screening; 8. Those with severe heart diseases, such as unstable angina pectoris, congestive heart failure (NYHA grade >= III), severe arrhythmia (QTc interval > 500 ms, corrected by Fridericia formula), uncontrolled hypertension (systolic pressure >= 160 mmHg or diastolic pressure >= 100 mmHg), etc.; 9. Female patients with abnormal menstruation due to organic gynecological diseases (such as uterine fibroids, endometriosis, and uterine adenomyosis, etc.); 10. Those who had or currently have severe life-threatening malignant tumor diseases, or patients with end-stage liver diseases; 11. Those who used DDAVP or blood-derived VWF-containing F? concentrate, blood-derived/recombinant VWF preparations, or antifibrinolytic drugs within 1 week before the first administration; 12. Those who used antithrombotic drugs within 1 week before the first administration; 13. Those who received fresh blood/plasma or cryoprecipitate treatment within 2 weeks before the first administration; 14. Those who received or planned to receive vaccination within 1 month before the first administration; 15. Those who underwent major surgery (surgery defined as grade III and IV surgeries) within 1 month before the first administration, or are scheduled to undergo surgery during the study; 16. Those who were enrolled in other clinical trials within 1 month before the first administration; 17. Those with a history of drug abuse or alcoholism (alcohol abuse criteria: long-term alcohol consumption exceeding 5 years, equivalent ethanol content >= 40g/d, or heavy alcohol consumption within 2 weeks, equivalent ethanol content > 80g/d. Ethanol content (g) conversion formula = alcohol consumption (mL) * ethanol content (%) * 0.8); 18. Those with mental illness or obvious mental disorders, or those with no capacity for behavior or cognition due to other reasons; 19. Those who have a fertility plan or sperm donation plan within 3 months after the first administration or are unwilling to take effective physical contraception measures (such as condoms,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Total annualized bleeding rate (ABR) after treatment at Week 24 and during the entire treatment period (including the treatment period and the extended treatment period); | — |
Secondary
| Measure | Time frame |
|---|---|
| Annualized spontaneous bleeding rate at Week 24 and during the entire treatment period (including observation period and subsequent follow-up period);Annualized traumatic bleeding rate at Week 24 and during the entire treatment period;Overall annualized bleeding rate, annualized spontaneous bleeding rate, and annualized traumatic bleeding rate at Week 24 and during the entire treatment period;EQ-5D-5L health questionnaire utility value at Week 24 of treatment, during the entire treatment period (including the treatment period and the extended treatment period); Change in EQ-VAS score from baseline at Week 24 of treatment, during the entire treatment period (including the treatment period and the extended treatment period); PK parameters after first dose:Tmax,Cmax,AUC0-t, etc.;Pharmacokinetic parameters after multiple doses: Tmax,ss, Cmax,ss, AUC0-t, CLss/F, Cmin,ss, Cav,ss, AUC0-t,ss, and steady-state fluctuation coefficient (DF), etc.; if data permits, parameters such as t1/2z, AUC0-8, Vz/F, MRT, and ?z will be calculated;Protac-APTT (Protac-induced protein C-activated APTT assay);protein C;prothrombin time (PT); | — |
Countries
China
Contacts
Public ContactHan Yue
The First Affiliated Hospital of Soochow University
Outcome results
None listed