Hemophilia A or B
Conditions
Brief summary
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.
Interventions
DRUGKN057
KN057 will be administered subcutaneously once a week.
Sponsors
Suzhou Alphamab Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. 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. 2. 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. 3. 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
1. Have serious or poorly controlled chronic diseases or obvious systemic diseases. 2. Have a history of thromboembolic disease, or currently have symptoms or signs related to thromboembolic disease or being treated with thrombolytic/antithrombotic therapy. 3. Have high-risk factors for thrombosis: such as atrial fibrillation, atherosclerotic diseases of important arteries, ischemic disease of important organs, vascular occlusive disease, autoimmune diseases with a high risk of thrombosis, or indwelling central venous catheter. 4. Known or suspected hypersensitivity to any constituent of the trial product or related products. 5. Have undergone major surgery (as determined by the investigator) within 3 months before screening, or have elective surgery planned during the study. 6. Used Emicizumab treatment within 6 months before screening. 7. Have received any gene therapy for hemophilia in the past. 8. Other factors that the investigator deems inappropriate for participating in this trial, such as the presence of concomitant diseases, treatment or examination abnormalities that affect the subject's safety during the trial or affect the interpretation of trial results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of TEAE. | Up to 12/26/56 weeks. | TEAE refers to 'treatment emergent adverse event'. |
| Incidence of TEAE related to the experimental drug. | Up to 12/26/56 weeks. | — |
| Incidence of SAE. | Up to 12/26/56 weeks. | SAE refers to 'serious adverse event'. |
| Incidence of thromboembolic events. | Up to 12/26/56 weeks. | — |
| Incidence of TMA and DIC. | Up to 12/26/56 weeks. | TMA refers to 'thrombotic microangiopathy'. DIC refers to 'disseminated intravascular coagulation'. |
| 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. | Up to 12/26/56 weeks. | — |
| Number of participants with clinically significant changes from baseline in physical exam. | Up to 12/26/56 weeks. | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | — |
| Incidence of anti-KN057 antibody (ADA) and neutralizing antibody (Nab). | Up to 12/26/56 weeks. | immunogenicity |
| 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. | Up to 12/26/56 weeks. | pharmacodynamics |
| Change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L). | Up to 26/52 weeks. | 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). |
| The annual usage of on-demand treatment drugs (adjusted by body weight). | Up to 26/52 weeks. | — |
Countries
China
Contacts
CONTACTYanrong Dong, Master
PRINCIPAL_INVESTIGATORRenchi Yang, Doctor
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
PRINCIPAL_INVESTIGATORHu Zhou, Doctor
Henan Cancer Hospital
PRINCIPAL_INVESTIGATORChangcheng Zheng, Doctor
The First Affiliated Hospital of USTC (Anhui Provincial Hospital)
PRINCIPAL_INVESTIGATORXielan Zhao
Xiangya Hospital of Central South University
PRINCIPAL_INVESTIGATORHongbo Cheng, Doctor
Jiangxi Provincial People's Hopital
PRINCIPAL_INVESTIGATORYanping Song, Doctor
Xi'an Central Hospital
PRINCIPAL_INVESTIGATORZeping Zhou, Doctor
The Second Affiliated Hospital of Kunming Medical University
PRINCIPAL_INVESTIGATORJie Yin, Doctor
The First Affiliated Hospital of Soochow University
PRINCIPAL_INVESTIGATORZhenyu Yan, Doctor
North China University of Science and Technology
PRINCIPAL_INVESTIGATORYun Chen, Doctor
Jinan Central Hospital
PRINCIPAL_INVESTIGATORYinsuo Zheng, Doctor
Bao Ji Central Hospital
PRINCIPAL_INVESTIGATORShu Chen, Doctor
The Second Affiliated Hospital of Chongqing Medical University
PRINCIPAL_INVESTIGATORYing Dong, Doctor
Maoming City People's Hospital
PRINCIPAL_INVESTIGATORXiaoli Wu, Doctor
The Second Hospital of Hebei Medical Hospital
PRINCIPAL_INVESTIGATORYanming Zhang, Doctor
Huai'an Second People'Hospital
PRINCIPAL_INVESTIGATORMiaoyong Zhu, Doctor
Wenzhou People's Hospital
PRINCIPAL_INVESTIGATORHaiping Yang, Doctor
The First Affiliated Hospital of Henan University of Science and Technology
PRINCIPAL_INVESTIGATORQingyi Wang, Doctor
The Fifth Affiliated Hospital of Anhui Medical
PRINCIPAL_INVESTIGATORWenqian Li, Doctor
Qinghai People's Hospital
Outcome results
None listed