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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
KN057 will be administered subcutaneously once a week.
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, China
RECRUITINGIncidence of TEAE.
TEAE refers to 'treatment emergent adverse event'.
Time frame: Up to 12/26/56 weeks.
Incidence of TEAE related to the experimental drug.
Time frame: Up to 12/26/56 weeks.
Incidence of SAE.
SAE refers to 'serious adverse event'.
Time frame: Up to 12/26/56 weeks.
Incidence of thromboembolic events.
Time frame: Up to 12/26/56 weeks.
Incidence of TMA and DIC.
TMA refers to 'thrombotic microangiopathy'. DIC refers to 'disseminated intravascular coagulation'.
Time frame: Up to 12/26/56 weeks.
Incidence of hypersensitivity type reactions.
Time frame: Up 12/26/56 weeks.
Incidence of injection site reactions.
Time frame: Up to 12/26/56 weeks.
Incidence of clinically significant laboratory value abnormalities.
Time frame: Up to 12/26/56 weeks.
Number of participants with clinically significant changes from baseline in electrocardiograms.
Time frame: Up to 12/26/56 weeks.
Number of participants with clinically significant changes from baseline in vital signs.
Time frame: Up to 12/26/56 weeks.
Number of participants with clinically significant changes from baseline in physical exam.
Time frame: Up to 12/26/56 weeks.
The exposure levels of KN057 after the first administration in both the new and old processes.
Time frame: Up to 12 weeks.
The steady-state trough concentrations of KN057 after the first administration in both the new and old processes.
Time frame: Up to 12 weeks.
Incidence of anti-KN057 antibody (ADA) and neutralizing antibody (Nab).
immunogenicity
Time frame: Up to 12/26/56 weeks.
Annualized bleeding rate (ABR) calculated based on treated spontaneous and traumatic bleeding episodes.
Time frame: Up to 26/52 weeks.
ABR calculated based on bleeding episodes, treated spontaneous bleeding episodes, treated joint bleeding episodes.
Time frame: 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.
Time frame: 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.
Time frame: Up to 26 weeks.
Levels of Free TFPI.
pharmacodynamics
Time frame: 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).
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Time frame: Up to 26/52 weeks.
The annual usage of on-demand treatment drugs (adjusted by body weight).
Time frame: Up to 26/52 weeks.