NCT06312475进行中（未招募）3 期
A Randomized, Open-label Study to Evaluate the Efficacy and Safety of KN057 Injection Prophylaxis in Patients With Hemophilia A or B With Inhibitors
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Annualized bleeding rate (ABR) calculated based on treated spontaneous and traumatic bleeding episodes in Arm 1 and Arm 2.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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;
- •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;
- •≥6 treated bleeding episodes within 26 weeks before screening;
- •Have not used TFPI antibody drugs before;
- •Be able and agree to elute prior drugs for the treatment of hemophilia.
排除标准
- •Have serious or poorly controlled chronic diseases or obvious systemic diseases;
- •Have a history of thromboembolic disease, or currently have symptoms or signs related to thromboembolic disease or being treated with thrombolytic/antithrombotic therapy;
- •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;
- •The presence of other inherited or acquired bleeding disorders other than hemophilia A and hemophilia B;
- •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);
- •Ongoing or planned Immune Tolerance Induction treatment;
- •When bleeding occurred in the past, rFVIIa was ineffective and PCC treatment must be used;
- •Known or suspected hypersensitivity to any constituent of the trial product or related products;
- •Have undergone major surgery (as determined by the investigator) within 3 months before screening, or have elective surgery planned during the study.
研究组 & 干预措施
Arm 1: KN057 Prophylaxis
Experimental
Successfully screened participants will be randomly assigned to KN057 Prophylaxis versus No Prophylaxis at a ratio of 2:1. Participants in Arm 1 (KN057 Prophylaxis) will receive KN057 through the main trial (26 weeks) and extension period (26 weeks) for total of approximately 1 year.
干预措施: KN057 (Drug)
Arm 2: No Prophylaxis
Experimental
Successfully screened participants will be randomly assigned to KN057 Prophylaxis versus No Prophylaxis at a ratio of 2:1. Participants in Arm 2 (No Prophylaxis) will continue on-demand treatment with their usual bypass agents (rFVIIa or PCC) through the main trial for 26 weeks, in the extension period they will switch to prophylaxis treatment and receive KN057 for 26 weeks.
干预措施: KN057 (Drug)
结局指标
主要结局
Annualized bleeding rate (ABR) calculated based on treated spontaneous and traumatic bleeding episodes in Arm 1 and Arm 2.
时间窗: From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total
Treated bleeding refers to the use of bypass agents and/or coagulation factors for hemostatic treatment of the bleeding.
次要结局
- ABR calculated based on bleeding episodes and treated bleeding episodes respectively in Arm 2.(From Day 183 (the beginning of the extension period) to Day 365 (the end of the extension period), approximately 26 weeks in total)
- ABR calculated based on bleeding episodes, treated bleeding episodes, treated spontaneous bleeding episodes, treated joint bleeding episodes, and treated target joint bleeding respectively in Arm 1.(From Day 1 (the beginning of the main trial) to Day 365 (the end of the extension period), approximately 52 weeks in total)
- Change from baseline in Hemophilia Joint Health Score (HJHS) scores in Arm 1 and Arm 2.(From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total)
- Change in HJHS scores from baseline in Arm 1 and from the 26th week in Arm 2.(From Day 1 (the beginning of the main trial) to Day 365 (the end of the extension period), approximately 52 weeks in total)
- Change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L) in Arm 1 and Arm 2.(From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total)
- Incidence of TEAE, TEAE related to the experimental drug and SAE.(From the signing of informed consent to 4 weeks after the last dose of KN057 (the end of the trial), approximately 59 weeks in total)
- Incidence of thromboembolic events, TMA and DIC.(From the signing of informed consent to 4 weeks after the last dose of KN057 (the end of the trial), approximately 59 weeks in total)
- ABR calculated based on bleeding episodes, treated spontaneous bleeding episodes, treated joint bleeding episodes, and treated target joint bleeding respectively in Arm 1 and Arm 2.(From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total)
- Change in EQ-5D-5L from baseline in Arm 1 and from the 26th week in Arm 2.(From Day 1 (the beginning of the main trial) to Day 365 (the end of the extension period), approximately 52 weeks in total)
- Incidence of hypersensitivity type reactions.(From the signing of informed consent to 4 weeks after the last dose of KN057 (the end of the trial), approximately 59 weeks in total)
- Incidence of injection site reactions.(From the signing of informed consent to 4 weeks after the last dose of KN057 (the end of the trial), approximately 59 weeks in total)
- Incidence of clinically significant laboratory value abnormalities.(From the signing of informed consent to 4 weeks after the last dose of KN057 (the end of the trial), approximately 59 weeks in total)
- Number of participants with clinically significant changes from baseline in physical exam.(From the signing of informed consent to 4 weeks after the last dose of KN057 (the end of the trial), approximately 59 weeks in total)
- Number of participants with clinically significant changes from baseline in electrocardiograms.(From the signing of informed consent to 4 weeks after the last dose of KN057 (the end of the trial), approximately 59 weeks in total)
- Number of participants with clinically significant changes from baseline in vital signs.(From the signing of informed consent to 4 weeks after the last dose of KN057 (the end of the trial), approximately 59 weeks in total)
- KN057 plasma trough concentration.(From start of KN057 treatment (Day 1 for KN057 prophylaxis group, Day 183 for no prophylaxis group) to 4 weeks after the last dose of KN057, approximately 56 weeks for KN057 prophylaxis group and 30 weeks for no prophylaxis group in total)
- Levels of Free TFPI.(From start of KN057 treatment (Day 1 for KN057 prophylaxis group, Day 183 for no prophylaxis group) to Day 365, approximately 52 weeks for KN057 prophylaxis group and 26 weeks for no prophylaxis group in total)
- Levels of prothrombin fragment 1+2 (PF1+2).(From start of KN057 treatment (Day 1 for KN057 prophylaxis group, Day 183 for no prophylaxis group) to Day 365, approximately 52 weeks for KN057 prophylaxis group and 26 weeks for no prophylaxis group in total)
- Incidence of anti-KN057 antibody (ADA) and neutralizing antibody (Nab).(From start of KN057 treatment (Day 1 for KN057 prophylaxis group, Day 183 for no prophylaxis group) to 4 weeks after the last dose of KN057, approximately 56 weeks for KN057 prophylaxis group and 30 weeks for no prophylaxis group in total)
研究者
研究点 (1)
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