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

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

The purpose of this study is to evaluate the safety, tolerability, immunogenicity , PK, and PD of a single dose of SR604 in participants with Hemophilia A or Hemophilia B, with or without inhibitors （Part A）and to evaluate the safety, PK, PD, and efficacy of multiple doses of SR604 in participants with Hemophilia A or Hemophilia B, or Factor VII (FVII) deficiency, with or without inhibitors (Part B and Part C).

Inclusion Criteria:

1. Age ≥18 years and ≤65 years at the time of signing informed consent, regardless of sex;

2. Clinically diagnosed with Hemophilia A or B or congenital coagulation Factor VII deficiency, and must meet the following criteria:

   1. Hemophilia A or B patients with historical or screening FVIII activity level <1% or FIX activity level ≤2%; Note: Hemophilia A or B patients with or without inhibitors may be enrolled. For patients without inhibitors (inhibitor titer <0.6 BU/mL), they must have previously received coagulation factor treatment with exposure days (EDs) >50 days.
   2. Congenital coagulation Factor VII deficiency patients with historical or screening FVII activity <10%;

3. Part A only: Received on-demand treatment with FVIII, FIX, recombinant human coagulation Factor VIIa (rFVIIa), or PCC for bleeding events within 1 month prior to screening;

4. Part B/Part C only: Accessible bleeding and treatment records (factor replacement or bypassing agent therapy) for at least 3 months prior to enrollment. Hemophilia A or B patients must have received on-demand treatment with ≥3 treated de novo bleeding episodes within 3 months prior to enrollment. Congenital coagulation Factor VII deficiency patients must have ≥2 treated de novo bleeding episodes within 3 months prior to enrollment;

5. No active bleeding symptoms prior to first dosing;

6. The subject or a legally acceptable representative has a full understanding of and can comply with the protocol requirements, has the willingness to complete the study as planned, and voluntarily agrees to provide biological samples for testing as required by the protocol;

7. The subject is able to understand the procedures and methods of this clinical trial, has been fully informed, and voluntarily participates in the trial by personally signing the informed consent form.

Exclusion Criteria:

1. Subjects with a known history of hypersensitivity to the investigational medicinal product or any of its components;

2. Intolerance to subcutaneous injection or presence of other local skin abnormalities or dermatological conditions that may affect administration and safety assessment;

3. Subjects meeting any of the following criteria at screening:

   1. Hemoglobin <60 g/L;
   2. Platelet count <100 × 10^9/L;
   3. 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;

4. Positive result(s) for hepatitis B virus surface antigen (HBsAg), anti-human immunodeficiency virus (HIV) antibody, and/or Treponema pallidum-specific antibody;

5. Clinically diagnosed with active hepatitis C;

6. 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;

7. Protein C deficiency or protein S deficiency;

8. History of or current thrombosis, family history of thrombosis, or history of thrombophilia prior to signing informed consent;

9. Intracranial hemorrhage due to Hemophilia A or B or congenital coagulation Factor VII deficiency within 2 years prior to screening;

10. 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);

11. 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;

12. 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;

13. Received whole blood or plasma therapy within 2 weeks prior to first dosing;

14. Received emicizumab treatment within 6 months prior to first dosing;

15. Received or planned to receive vaccination within 4 weeks prior to first dosing or during the trial;

16. Underwent major surgery (e.g., orthopedic surgery, abdominal surgery) within 1 month prior to first dosing, or planned to undergo surgery during the study;

17. Enrolled in another clinical trial within 1 month prior to first dosing;

18. 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);

19. Psychiatric illness or significant mental impairment, or incapacity or lack of cognitive ability due to other reasons;

20. 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);

21. 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);

22. 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.