A Phase II Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of SR604 Injection in Patients With Von Willebrand Disease

Exclusion Criteria25

• Known history of hypersensitivity to the investigational drug formulation or any of its components;
• Intolerance to subcutaneous injection or presence of other local skin abnormalities or dermatological conditions that may affect drug administration and safety assessment;
• Meeting any of the following criteria at screening:
• Hemoglobin < 60 g/L;
• Platelet count < 80 x 10\^9/L;
• Hepatic or renal dysfunction: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >= 2.5 x upper limit of normal (ULN), or total bilirubin >= 1.5 x ULN; or serum creatinine (Cr) >= 1.5 x ULN;
• Positive for anti-human immunodeficiency virus (HIV) antibody;
• Presence of any bleeding disorder other than von Willebrand disease \[hemophilia A or B, congenital coagulation factor VII deficiency, acquired von Willebrand disease (AVWS), platelet-type VWD, inherited platelet disorders, etc.\]; or significantly abnormal coagulation parameters due to diseases other than von Willebrand disease (e.g., platelet disorders, vitamin K deficiency, etc.);
• Presence of protein C deficiency or protein S deficiency;
• History of thrombosis or family history of thrombosis prior to signing informed consent or currently, or history of thrombophilia;
• Severe bleeding due to VWD within 2 years prior to screening, such as intracranial hemorrhage, esophageal variceal bleeding, etc.;
• Severe cardiac disease, such as unstable angina, congestive heart failure (New York Heart Association class >= III), severe arrhythmia (QTc interval > 500 ms, corrected by Fridericia formula), uncontrolled hypertension (systolic blood pressure >= 160 mmHg or diastolic blood pressure >= 100 mmHg), etc.;
• Female patients with menstrual abnormalities due to organic gynecological diseases (e.g., uterine fibroids, endometriosis, adenomyosis, etc.);
• Previous or current life-threatening malignant neoplasms or end-stage liver disease;
• Use of DDAVP or plasma-derived VWF-containing factor VIII concentrate, plasma-derived/recombinant VWF preparations, or antifibrinolytic therapy within 1 week prior to the first dose;
• Use of antithrombotic agents within 1 week prior to the first dose;
• Receipt of fresh blood/plasma or cryoprecipitate therapy within 2 weeks prior to the first dose;
• Receipt of vaccination within 1 month prior to the first dose or planned vaccination during the study period;
• Major surgery (major surgery defined as Grade III and IV surgeries) within 1 month prior to the first dose, or planned surgery during the study period;
• Enrollment in other clinical trials within 1 month prior to the first dose;
• History of drug abuse or alcohol dependence (alcohol dependence criteria: long-term drinking history exceeding 5 years, equivalent ethanol intake >= 40 g/day, or heavy drinking within 2 weeks, equivalent ethanol intake > 80 g/day. Ethanol amount (g) conversion formula = alcohol consumption (mL) x alcohol content (%) x 0.8);
• Presence of psychiatric disease or significant mental disorder, or other reasons resulting in incapacity or lack of cognitive ability;
• Plans for procreation or sperm donation throughout the study period up to 3 months after the last dose, or unwillingness to use effective physical contraceptive measures (e.g., condoms);
• Presence of clinically significant disease or other reasons rendering the patient unsuitable for clinical trial participation in the investigator's opinion (e.g., patient unlikely to benefit from the clinical trial);
• Patients whom the investigator considers to have poor compliance, rendering efficacy evaluation difficult or likelihood of completing the planned treatment course and follow-up low.