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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A：Experimental group | Experimental | Successfully screened participants in Part A will be randomly assigned to Experimental group versus Control group at a ratio of 2:1. Participants in Experimental group will receive KN057 prophylaxis through the main trial (26 weeks) and extension period (26 weeks) for total of approximately 1 year. |
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| Part A：Control group | Experimental | Successfully screened participants in Part A will be randomly assigned to Experimental group versus Control group at a ratio of 2:1. Participants in Control group will continue on-demand treatment with coagulation factor 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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| Part B：Prophylaxis group | Experimental | Successfully screened participants in Part B will be nonrandomly assigned to Prophylaxis group. Participants in Prophylaxis group will continue prophylaxis with coagulation factor for the first 26 weeks (the factor period), then they will switch to prophylaxis with KN057 for the last 26 weeks (the KN057 period). |
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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 |
|---|---|---|
| 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. | 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. | From Week 1 to Week 26, through the factor period. From Week 27 to Week 52, through the KN057 period. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Participants who are enrolled into Part A must also meet the following criteria:
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:
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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 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. | 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. | 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. | 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. | 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. | 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. | 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 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). | 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. | 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 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'. | 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 concentration. | pharmacokinetics | From start of KN057 treatment (Week 1 for Experimental group, Week 26 for Control group and Prophylaxis group) to 4 weeks after the last dose of KN057, approximately 56 weeks for Experimental group and 30 weeks for Control group and Prophylaxis group. |
| Levels of Total TFPI. | pharmacodynamics | From start of KN057 treatment (Week 1 for Experimental group, Week 26 for Control group and Prophylaxis group) to 4 weeks after the last dose of KN057, approximately 56 weeks for Experimental group and 30 weeks for Control group and Prophylaxis group. |
| Levels of Free TFPI. | pharmacodynamics | From start of KN057 treatment (Week 1 for Experimental group, Week 26 for Control group and Prophylaxis group) to 4 weeks after the last dose of KN057, approximately 56 weeks for Experimental group and 30 weeks for Control group and Prophylaxis group. |
| Levels of prothrombin fragment 1+2 (PF1+2). | pharmacodynamics | From start of KN057 treatment (Week 1 for Experimental group, Week 26 for Control group and Prophylaxis group) to 4 weeks after the last dose of KN057, approximately 56 weeks for Experimental group and 30 weeks for Control group and Prophylaxis group. |
| Incidence of anti-KN057 antibody (ADA) and neutralizing antibody (Nab). | immunogenicity | From start of KN057 treatment (Week 1 for Experimental group, Week 26 for Control group and Prophylaxis group) to 4 weeks after the last dose of KN057, approximately 56 weeks for Experimental group and 30 weeks for Control group and Prophylaxis group. |
| Zeping Zhou, Doctor | The Second Affiliated Hospital of Kunming Medical University | Principal Investigator |
| Runhui Wu, Doctor | Beijing Children's Hospital | 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 |
| Ziqiang Yu, Doctor | The First Affiliated Hospital of Soochow University | Principal Investigator |
| Yun Chen, Doctor | Qianfoshan Hospital | Principal Investigator |
| Pingchong Lei, Doctor | Henan Provincial People's Hospital | Principal Investigator |
| Yinsuo Zheng, Doctor | Bao Ji Central Hospital | Principal Investigator |
| Peng Cheng, Doctor | First Affiliated Hospital of Guangxi Medical University | Principal Investigator |
| Jianwen Xiao, Doctor | Children's Hospital of Chongqing Medical University | Principal Investigator |
| Ruibin Huang, Doctor | The First Affiliated Hospital of Nanchang University | Principal Investigator |
| Hailiang Li, Doctor | The first affiliated hospital of jiangxi medical college | Principal Investigator |
| Shu Chen, Doctor | The Second Affiliated Hospital of Chongqing Medical University | Principal Investigator |
| Xiong Zhang, Doctor | Maoming City People's Hospital | Principal Investigator |
| Jingyu Zhang, Doctor | The Second Hospital of Hebei Medical Hospital | Principal Investigator |
| Baolai Hua, Doctor | Beijing Shijitan Hospital, Capital Medical University | Principal Investigator |
| Yanming Zhang, Doctor | Huai'an Second People'Hospital | Principal Investigator |