Efficacy and Safety of KN057 Prophylaxis in Patients With Haemophilia A or B With Inhibitors

A Randomized, Open-label Study to Evaluate the Efficacy and Safety of KN057 Injection Prophylaxis in Patients With Hemophilia A or B With Inhibitors

The purpose of this study is to show that KN057 can prevent bleeds in patients with haemophilia A or B with inhibitors and is safe to use. Successfully screened participants will be randomly assigned to KN057 Prophylaxis (Arm 1) versus No Prophylaxis (Arm 2) at a ratio of 2:1. Participants in KN057 Prophylaxis will receive KN057 prophylaxis for 52 weeks upon enrollment. Participants in No Prophylaxis will first receive on-demand treatment for 26 weeks, then switch to KN057 prophylaxis for 26 weeks.The trial period is 59 weeks, including a 3-week screening period, a 26-week main trial, a 26-week extension period, and a 4-week follow-up period after the last administration.

Inclusion Criteria:

1. Male, 12 to 70 years old at the time of signing informed consent (including the cut-off value), body weight ≥25 kg and BMI <28 kg/m^2 at screening;
2. The FVIII or FIX inhibitor test is positive at a high titer (≥5 BU/ml) during the screening period; or the FVIII or FIX inhibitor is detected at a low titer (0.6 BU/ml or the upper limit of normal value < inhibitor titer < 5 BU/ml) during the screening period and treatment with bypass agents (rFVIIa or PCC) has been started;
3. ≥6 treated bleeding episodes within 26 weeks before screening;
4. Have not used TFPI antibody drugs before;
5. Be able and agree to elute prior drugs for the treatment of hemophilia.

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. 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);
6. Ongoing or planned Immune Tolerance Induction treatment;
7. When bleeding occurred in the past, rFVIIa was ineffective and PCC treatment must be used;
8. Known or suspected hypersensitivity to any constituent of the trial product or related products;
9. Have undergone major surgery (as determined by the investigator) within 3 months before screening, or have elective surgery planned during the study.