An Open-label, Multicenter Phase I/II Clinical Trial to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetic/Pharmacodynamic (PK/PD) Characteristics of SR604 Injection in Patients With Hemophilia A/B and Congenital Factor VII Deficiency

Exclusion Criteria25

• Subjects with a known history of hypersensitivity to the investigational medicinal product or any of its components;
• Intolerance to subcutaneous injection or presence of other local skin abnormalities or dermatological conditions that may affect administration and safety assessment;
• Subjects meeting any of the following criteria at screening:
• Hemoglobin <60 g/L;
• Platelet count <100 × 10\^9/L;
• Hepatic or renal impairment: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.5 × upper limit of normal (ULN), or total bilirubin ≥1.5 × ULN; or serum creatinine (Cr) ≥1.5 × ULN;
• Positive result(s) for hepatitis B virus surface antigen (HBsAg), anti-human immunodeficiency virus (HIV) antibody, and/or Treponema pallidum-specific antibody;
• Clinically diagnosed with active hepatitis C;
• Any other bleeding disorder or any other disease causing significant coagulation abnormalities (e.g., platelet disorders, vitamin K deficiency, etc.) other than Hemophilia A or B and congenital coagulation Factor VII deficiency;
• Protein C deficiency or protein S deficiency;
• History of or current thrombosis, family history of thrombosis, or history of thrombophilia prior to signing informed consent;
• Intracranial hemorrhage due to Hemophilia A or B or congenital coagulation Factor VII deficiency within 2 years prior to screening;
• Severe cardiac disease, such as unstable angina, congestive heart failure (New York Heart Association Class ≥III), severe arrhythmia (QTc interval >450 ms, corrected by Fridericia's formula), or uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥95 mmHg);
• Received recombinant human coagulation Factor VIIa (rFVIIa) within 48 hours prior to first dosing; received any FVIII-containing product within 72 hours prior to first dosing; received any FIX-containing product within 96 hours prior to first dosing; long-acting products of the above have not completed a washout of 5 half-lives;
• Used or requires use of any anticoagulant, antifibrinolytic agent, or chemical drug, biological product, or traditional Chinese medicine affecting platelet function, including nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, within 1 week prior to first dosing or during the trial;
• Received whole blood or plasma therapy within 2 weeks prior to first dosing;
• Received emicizumab treatment within 6 months prior to first dosing;
• Received or planned to receive vaccination within 4 weeks prior to first dosing or during the trial;
• Underwent major surgery (e.g., orthopedic surgery, abdominal surgery) within 1 month prior to first dosing, or planned to undergo surgery during the study;
• Enrolled in another clinical trial within 1 month prior to first dosing;
• History of drug abuse or alcoholism (alcoholism criteria: long-term drinking history exceeding 5 years, equivalent to ethanol intake ≥40 g/day, or heavy drinking within 2 weeks, equivalent to ethanol intake >80 g/day. Ethanol amount (g) conversion formula = alcohol volume (mL) × ethanol content (%) × 0.8);
• Psychiatric illness or significant mental impairment, or incapacity or lack of cognitive ability due to other reasons;
• Plans to have children or donate sperm during the entire trial period up to 6 months after the last dose, or unwilling to use effective physical contraceptive measures (e.g., condoms);
• Subjects with clinically significant disease or other conditions that the investigator considers unsuitable for participation in the clinical trial (e.g., the patient cannot benefit from the clinical trial);
• Subjects deemed by the investigator to have poor compliance, rendering efficacy evaluation impossible or with low likelihood of completing the planned treatment course and follow-up.