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The purposes of this open-label, multicenter III clinical trial are to evaluate the safety and efficacy of long-term preventive treatment with KN057 in Haemophilia A or B patients with or without inhibitors, and to assess the pharmacokinetic characteristics of the new and old processes KN057.
The participants in Part PK will be randomly assigned to Old process Group or New process Group in a 1:1 ratio. The participants in Old process Group will receive old process KN057 prophylaxis for the first 26 weeks and new process KN057 prophylaxis for the following 26 weeks. The participants in New process Group will receive new process KN057 prophylaxis for both the first 26 weeks and the last 26 weeks.
The participants in Part non-PK will be non-randomized and treated with new process KN057 for 52 weeks prophylaxis after enrollment.
Priority screening and enrollment of participants who have participated in the KN057-A-301 or KN057-A-302 study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part PK # Old process Group | Experimental | The participants in Old process Group will receive old process KN057 prophylaxis for the first 26 weeks and new process KN057 prophylaxis for the following 26 weeks. |
|
| Part PK # New process Group | Experimental | The participants in New process Group will receive new process KN057 prophylaxis for both the first 26 weeks and the last 26 weeks. |
|
| Part non-PK | Experimental | The participants in Part non-PK will be treated with new process KN057 for 52 weeks prophylaxis after enrollment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KN057 | Drug | KN057 will be administered subcutaneously once a week. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of TEAE. | TEAE refers to 'treatment emergent adverse event'. | Up to 12/26/56 weeks. |
| Incidence of TEAE related to the experimental drug. | Up to 12/26/56 weeks. | |
| Incidence of SAE. | SAE refers to 'serious adverse event'. | Up to 12/26/56 weeks. |
| Incidence of thromboembolic events. | Up to 12/26/56 weeks. | |
| Incidence of TMA and DIC. | TMA refers to 'thrombotic microangiopathy'. DIC refers to 'disseminated intravascular coagulation'. | Up to 12/26/56 weeks. |
| Incidence of hypersensitivity type reactions. | Up 12/26/56 weeks. | |
| Incidence of injection site reactions. | Up to 12/26/56 weeks. | |
| Incidence of clinically significant laboratory value abnormalities. | Up to 12/26/56 weeks. | |
| Number of participants with clinically significant changes from baseline in electrocardiograms. | Up to 12/26/56 weeks. | |
| Number of participants with clinically significant changes from baseline in vital signs. |
| Measure | Description | Time Frame |
|---|---|---|
| The exposure levels of KN057 after the first administration in both the new and old processes. | Up to 12 weeks. | |
| The steady-state trough concentrations of KN057 after the first administration in both the new and old processes. | Up to 12 weeks. |
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Inclusion Criteria:
Male, 12 to 65 years old at the time of signing informed consent, body weight ≥30 kg and BMI <28 kg/m^2 at screening.
For participates with inhibitors: Tested positive for high-titer FVIII or FIX inhibitors (≥ 5 BU/mL) at screening; or tested positive for low-titer FVIII or FIX inhibitors (0.6 BU/mL or upper limit of normal [ULN] < inhibitor titer < 5 BU/mL) at screening, with ongoing treatment using bypassing agents (rFVIIa or PCC).
For participates without inhibitors: Severe and moderately severe hemophilia A or hemophilia B (FVIII or FIX activity level ≤2%); 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; There is no history of FVIII or FIX inhibitors in the past, or there has been an inhibitor, but the inhibitor has turned negative for at least 5 years before screening and has not reappeared (no positive inhibitor was detected); Use coagulation factor replacement therapy for no less than 100 exposure days before screening.
Participates with inhibitors agree to avoid using PCC for treatment when breakthrough bleeding occurred. Participates without inhibitors agree to be treated with standard half-life coagulation factors (FVIII or FIX) in the event of breakthrough bleeding.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yanrong Dong, Master | Contact | +86 18914005458 | yanrongdong@alphamab.com |
| Name | Affiliation | Role |
|---|---|---|
| Renchi Yang, Doctor | Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences | Principal Investigator |
| Hu Zhou, Doctor | Henan Cancer Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences | Recruiting | Tianjin | Tianjin Municipality | 300020 | China |
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| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| Up to 12/26/56 weeks. |
| Number of participants with clinically significant changes from baseline in physical exam. | Up to 12/26/56 weeks. |
| Incidence of anti-KN057 antibody (ADA) and neutralizing antibody (Nab). | immunogenicity | Up to 12/26/56 weeks. |
| Annualized bleeding rate (ABR) calculated based on treated spontaneous and traumatic bleeding episodes. | Up to 26/52 weeks. |
| ABR calculated based on bleeding episodes, treated spontaneous bleeding episodes, treated joint bleeding episodes. | Up to 26/52 weeks. |
| The correlation between the steady-state trough concentrations of KN057 and the incidence of TEAE related to the experimental drug. | Up to 26 weeks. |
| The correlation between the steady-state trough concentrations of KN057 and ABR calculated based on treated spontaneous and traumatic bleeding episodes. | Up to 26 weeks. |
| Levels of Free TFPI. | pharmacodynamics | Up to 12/26/56 weeks. |
| Change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L). | 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). | Up to 26/52 weeks. |
| The annual usage of on-demand treatment drugs (adjusted by body weight). | Up to 26/52 weeks. |
| Changcheng Zheng, Doctor | The First Affiliated Hospital of USTC (Anhui Provincial Hospital) | Principal Investigator |
| Xielan Zhao | Xiangya Hospital of Central South University | Principal Investigator |
| Hongbo Cheng, Doctor | Jiangxi Provincial People's Hopital | Principal Investigator |
| Yanping Song, Doctor | Xi'an Central Hospital | Principal Investigator |
| Zeping Zhou, Doctor | The Second Affiliated Hospital of Kunming Medical University | Principal Investigator |
| Jie Yin, Doctor | The First Affiliated Hospital of Soochow University | Principal Investigator |
| Zhenyu Yan, Doctor | North China University of Science and Technology | Principal Investigator |
| Yun Chen, Doctor | Jinan Central Hospital | Principal Investigator |
| Yinsuo Zheng, Doctor | Bao Ji Central Hospital | Principal Investigator |
| Shu Chen, Doctor | The Second Affiliated Hospital of Chongqing Medical University | Principal Investigator |
| Ying Dong, Doctor | Maoming City People's Hospital | Principal Investigator |
| Xiaoli Wu, Doctor | The Second Hospital of Hebei Medical Hospital | Principal Investigator |
| Yanming Zhang, Doctor | Huai'an Second People'Hospital | Principal Investigator |
| Miaoyong Zhu, Doctor | Wenzhou People's Hospital | Principal Investigator |
| Haiping Yang, Doctor | The First Affiliated Hospital of Henan University of Science and Technology | Principal Investigator |
| Qingyi Wang, Doctor | The Fifth Affiliated Hospital of Anhui Medical | Principal Investigator |
| Wenqian Li, Doctor | Qinghai People's Hospital | Principal Investigator |
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |