Efficacy and Safety of KN057 Prophylaxis in Patients With Haemophilia A or B Without Inhibitors

A Randomized, Open-label Study to Evaluate the Efficacy and Safety of KN057 Injection Prophylaxis in Patients With Hemophilia A or B Without Inhibitors

The purpose of this study is to show that KN057 can prevent bleeds in patients with haemophilia A or B without inhibitors and is safe to use. Participants receiving on-demand treatment prior to screening will be randomly assigned to Experimental group or Control group at a ratio of 2:1 in Part A. Participants receiving prophylaxis prior to screening will be nonrandomly assigned to Prophylaxis group in Part B. Participants in Experimental group will receive KN057 prophylaxis for 52 weeks upon enrollment. Participants in Control group will first receive on-demand treatment for 26 weeks, then switch to KN057 prophylaxis for 26 weeks. Participants in Prophylaxis group will first receive prophylaxis with coagulation factor for 26 weeks, then switch to KN057 prophylaxis for 26 weeks.

Inclusion Criteria:

1. Male, 12 to 70 years old at the time of signing informed consent (including the cut-off value), body weight ≥30 kg and BMI <28 kg/m^2 at screening;
2. Severe and moderately severe hemophilia A or hemophilia B (FVIII or FIX activity level ≤2%);
3. FVIII or FIX inhibitor test is negative (<0.6 BU/ml) or lower than the lower limit of laboratory normal values during the screening period;
4. There is no history of FVIII or FIX inhibitors in the past; or there has been an inhibitor, but it has been at least 5 years since successful immune tolerance induction therapy (ITI), and the inhibitor has not reappeared (a positive inhibitor was detected after successful ITI);
5. Use coagulation factor replacement therapy for no less than 100 exposure days before screening;
6. Have not used Anti-TFPI drugs before;
7. Be able and agree to elute the original hemophilia drugs.

Participants who are enrolled into Part A must also meet the following criteria:

1. ≥6 treated bleeding episodes within 26 weeks before screening;
2. Receiving on-demand treatment, non-standard prophylaxis, or standard prophylaxis no more than 12 weeks before screening;

Participants who are enrolled into Part B must also meet the following criteria:

Being on standard prophylaxis and maintaining it for more than 12 weeks (standard prophylaxis is defined as at least 80% compliance with a predetermined prophylaxis regimen).

Exclusion Criteria:

1. Have serious or poorly controlled chronic diseases or obvious systemic diseases;
2. Have a history of thromboembolic disease, or currently have symptoms or signs related to thromboembolic disease or being treated with thrombolytic/antithrombotic therapy;
3. Have high-risk factors for thrombosis: such as a history of coronary atherosclerotic disease, ischemic disease of important organs, vascular occlusive disease, autoimmune diseases with a high risk of thrombosis, or indwelling central venous catheter;
4. The presence of other inherited or acquired bleeding disorders other than hemophilia A and hemophilia B;
5. Known or suspected hypersensitivity to any constituent of the trial product or related products;
6. Have undergone major surgery (as determined by the investigator) within 3 months before screening, or have elective surgery planned during the study;
7. Used Emicizumab treatment within 6 months before screening;
8. Have received any gene therapy for hemophilia in the past;
9. Other factors that the investigator deems inappropriate for participating in this trial, such as the presence of concomitant diseases, treatment or examination abnormalities that affect the subject's safety during the trial or affect the interpretation of trial results.