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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KN057 | Drug | KN057 will be administered subcutaneously once a week. |
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| Measure | Description | Time Frame |
|---|---|---|
| Annualized bleeding rate (ABR) calculated based on treated spontaneous and traumatic bleeding episodes in Arm 1 and Arm 2. | Treated bleeding refers to the use of bypass agents and/or coagulation factors for hemostatic treatment of the bleeding. | From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Bleeding episodes includes spontaneous and/or traumatic bleeding episodes, excluding surgery/procedure-related bleeding episodes. Treated bleeding refers to the use of bypass agents and/or coagulation factors for hemostatic treatment of the bleeding. Target joint are those with spontaneous bleeding ≥3 times in the 6 months prior to screening. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Renchi Yang, Doctor | Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences | Principal Investigator |
| Jing Sun, Doctor | Nanfang Hospital, Southern Medical University | Principal Investigator |
| Hu Zhou, Doctor | Henan Cancer Hospital | Principal Investigator |
| Changcheng Zheng, Doctor | The First Affiliated Hospital of USTC (Anhui Provincial Hospital) | Principal Investigator |
| Xielan Zhao, Doctor | Xiangya Hospital of Central South University | Principal Investigator |
| Lili Chen, Doctor | Tai Zhou First People's Hospital | Principal Investigator |
| Chenghao Jin, Doctor | Jiangxi Provincial People's Hopital | Principal Investigator |
| Yanping Song, Doctor | Xi'an Central Hospital | Principal Investigator |
| Yaming Xi, Doctor | LanZhou University |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences | Tianjin | Tianjin Municipality | 300020 | China |
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| From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total |
| ABR calculated based on bleeding episodes and treated bleeding episodes respectively in Arm 2. | Bleeding episodes includes spontaneous and/or traumatic bleeding episodes, excluding surgery/procedure-related bleeding episodes. Treated bleeding refers to the use of bypass agents and/or coagulation factors for hemostatic treatment of the bleeding. | 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. | Bleeding episodes includes spontaneous and/or traumatic bleeding episodes, excluding surgery/procedure-related bleeding episodes. Treated bleeding refers to the use of bypass agents and/or coagulation factors for hemostatic treatment of the bleeding. Target joint are those with spontaneous bleeding ≥3 times in the 6 months prior to screening. | 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. | 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. | 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. | 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. | 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. | 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). | 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. | 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). | 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 TEAE, TEAE related to the experimental drug and SAE. | TEAE refers to 'treatment emergent adverse event'. SAE refers to 'serious adverse event'. | 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. | TMA refers to 'thrombotic microangiopathy'. DIC refers to 'disseminated intravascular coagulation'. | 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 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. | pharmacokinetics | 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. | pharmacodynamics | 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). | pharmacodynamics | 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). | immunogenicity | 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 |
| Zeping Zhou, Doctor | The Second Affiliated Hospital of Kunming Medical University | Principal Investigator |
| Runhui Wu, Doctor | Beijing Children's Hospital | Principal Investigator |
| Ziqiang Yu, Doctor | The First Affiliated Hospital of Soochow University | Principal Investigator |
| Jingyu Yan, Doctor | North China University of Science and Technology | Principal Investigator |
| Sujun Gao, Doctor | Bethune First Hospital of Jilin University | Principal Investigator |
| Wei Yang, Doctor | Shengjing Hospital of China University | Principal Investigator |
| Rong Zhou, Doctor | The Third People's Hospital of Chengdu | Principal Investigator |