NCT06569108 - Efficacy and Safety of KN057 Prophylaxis in Patients With Haemophilia A or B Without Inhibitors | Crick

Eligibility

Sex: MALEMin age: 12 YearsMax age: 70 Years

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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.

Outcomes

Primary Outcomes

Part A: Annualized bleeding rate (ABR) calculated based on treated spontaneous and traumatic bleeding episodes in Experimental group and Control group.

Treated bleeding refers to the use of coagulation factors for hemostatic treatment of the bleeding.

Time frame: From Week 1 to Week 26, through the main trial.

Part B: ABR calculated based on treated spontaneous and traumatic bleeding episodes in Prophylaxis group.

Treated bleeding refers to the use of coagulation factors for hemostatic treatment of the bleeding.

Time frame: From Week 1 to Week 26, through the factor period. From Week 27 to Week 52, through the KN057 period.

Secondary Outcomes

ABR calculated based on bleeding episodes, treated spontaneous and traumatic bleeding episodes, treated spontaneous bleeding episodes, treated joint bleeding episodes, and treated target joint bleeding respectively in Experimental group.

Bleeding episodes includes spontaneous and/or traumatic bleeding episodes, excluding surgery/procedure-related bleeding episodes. Treated bleeding refers to the use of coagulation factors for hemostatic treatment of the bleeding. Target joint are those with spontaneous bleeding ≥3 times in the 6 months prior to screening.

Time frame: From Week 1 to Week 52, through the main trial and extension period.

ABR calculated based on bleeding episodes, treated spontaneous bleeding episodes, treated joint bleeding episodes, and treated target joint bleeding respectively in Experimental group, Control group and Prophylaxis group.

Time frame: From Week 1 to Week 26. From Week 27 to Week 52.

Proportion of participants with untreated bleeding episodes in Experimental group, Control group and Prophylaxis group.

Treated bleeding refers to the use of coagulation factors for hemostatic treatment of the bleeding.

Time frame: From Week 1 to Week 26. From Week 27 to Week 52.

The annual usage of on-demand treatment drugs (adjusted by body weight) in Experimental group and Control group.

Time frame: From Week 1 to Week 26. From Week 27 to Week 52.

Change from baseline in Hemophilia Joint Health Score (HJHS) scores in Experimental group, Control group and Prophylaxis group.

Hemophilia Joint Health Scores (HJHS) is a validated 11-item scoring tool developed for the assessment of joint health in participants with hemophilia. It comprised an evaluation of the elbows, knee and ankle joints: swelling (0 to 3), duration of swelling (0 and 1), muscle atrophy (0 to 2), crepitus on motion (0 to 2), flexion loss (0 to 3), extension loss (0 to 3), joint pain (0 to 2) and strength (0 to 4), in each item 0 = none and higher score = severe damage and global gait (walking, stairs, running, hopping on 1 leg) scored on scale ranged from 0 to 4, where 0 = all skills in normal limit and 4 = no skills within normal limits). Total HJHS score = sum of joint totals (0 to 120) + general gait (1 to 4) and ranged from 0 (no joint damage) to 124 (severe joint damage), where higher score indicated severe joint damage.

Time frame: From Week 1 to Week 26.

Change in HJHS scores from baseline in Experimental group, from the 26th week in Control group, from baseline and the 26th week in Prophylaxis group.

Time frame: From Week 1 to Week 52.

Change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L) in Experimental group, Control group and Prophylaxis group.

The EQ-5D-5L questionnaire is made up for 2 components, health state description and evaluation. In description part, health status is measured in terms of 5 dimensions (5D): mobility, self-care, usual activities, pain/discomfort, and anxiety/depression; every dimension contains 5 levels (5L): no difficulty, a little difficulty, moderate difficulty, severe difficulty, very severe difficulty/inability to perform. In evaluation part, the respondents evaluate their overall health status using the visual analogue scale (EQ-VAS) ranging from 0 (worst imaginable health) to 100 (best imaginable health).

Time frame: From Week 1 to Week 26.

Change in EQ-5D-5L from baseline in Experimental group, from the 26th week in Control group, from baseline and the 26th week in Prophylaxis group.

Time frame: From Week 1 to Week 52.

Incidence of TEAE, TEAE related to the experimental drug and SAE.

TEAE refers to 'treatment emergent adverse event'. SAE refers to 'serious adverse event'.