Clinical trial NCT06312475: Efficacy and Safety of KN057 Prophylaxis in Patients With Haemophilia A or B With Inhibitors
Official title: A Randomized, Open-label Study to Evaluate the Efficacy and Safety of KN057 Injection Prophylaxis in Patients With Hemophilia A or B With Inhibitors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hemophilia A With Inhibitor
Hemophilia B With Inhibitor
Lead sponsor: Suzhou Alphamab Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-03-15
Enrollment: 51
Sex: MALE
Minimum age (years): 12
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Male, 12 to 70 years old at the time of signing informed consent (including the cut-off value), body weight ≥25 kg and BMI \<28 kg/m\^2 at screening;
2. The FVIII or FIX inhibitor test is positive at a high titer (≥5 BU/ml) during the screening period; or the FVIII or FIX inhibitor is detected at a low titer (0.6 BU/ml or the upper limit of normal value \< inhibitor titer \< 5 BU/ml) during the screening period and treatment with bypass agents (rFVIIa or PCC) has been started;
3. ≥6 treated bleeding episodes within 26 weeks before screening;
4. Have not used TFPI antibody drugs before;
5. Be able and agree to elute prior drugs for the treatment of hemophilia.

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 a history of coronary atherosclerotic disease, ischemic disease of important organs, vascular occlusive disease, autoimmune diseases with a high risk of thrombosis, or indwelling central venous catheter;
4. The presence of other inherited or acquired bleeding disorders other than hemophilia A and hemophilia B;
5. 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);
6. Ongoing or planned Immune Tolerance Induction treatment;
7. When bleeding occurred in the past, rFVIIa was ineffective and PCC treatment must be used;
8. Known or suspected hypersensitivity to any constituent of the trial product or related products;
9. Have undergone major surgery (as determined by the investigator) within 3 months before screening, or have elective surgery planned during the study.

Primary outcomes:
measure: Annualized bleeding rate (ABR) calculated based on treated spontaneous and traumatic bleeding episodes in Arm 1 and Arm 2.
timeFrame: From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total
Secondary outcomes:
measure: 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.
timeFrame: From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total
measure: ABR calculated based on bleeding episodes and treated bleeding episodes respectively in Arm 2.
timeFrame: From Day 183 (the beginning of the extension period) to Day 365 (the end of the extension period), approximately 26 weeks in total
measure: 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.
timeFrame: From Day 1 (the beginning of the main trial) to Day 365 (the end of the extension period), approximately 52 weeks in total
measure: Change from baseline in Hemophilia Joint Health Score (HJHS) scores in Arm 1 and Arm 2.
timeFrame: From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total
measure: Change in HJHS scores from baseline in Arm 1 and from the 26th week in Arm 2.
timeFrame: From Day 1 (the beginning of the main trial) to Day 365 (the end of the extension period), approximately 52 weeks in total
measure: Change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L) in Arm 1 and Arm 2.
timeFrame: From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total
measure: Change in EQ-5D-5L from baseline in Arm 1 and from the 26th week in Arm 2.
timeFrame: From Day 1 (the beginning of the main trial) to Day 365 (the end of the extension period), approximately 52 weeks in total
measure: Incidence of TEAE, TEAE related to the experimental drug and SAE.
timeFrame: 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
measure: Incidence of thromboembolic events, TMA and DIC.
timeFrame: 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
measure: Incidence of hypersensitivity type reactions.
timeFrame: 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
measure: Incidence of injection site reactions.
timeFrame: 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
measure: Incidence of clinically significant laboratory value abnormalities.
timeFrame: 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
measure: Number of participants with clinically significant changes from baseline in physical exam.
timeFrame: 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
measure: Number of participants with clinically significant changes from baseline in electrocardiograms.
timeFrame: 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
measure: Number of participants with clinically significant changes from baseline in vital signs.
timeFrame: 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
measure: KN057 plasma trough concentration.
timeFrame: 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
measure: Levels of Free TFPI.
timeFrame: 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
measure: Levels of prothrombin fragment 1+2 (PF1+2).
timeFrame: 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
measure: Incidence of anti-KN057 antibody (ADA) and neutralizing antibody (Nab).
timeFrame: 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
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
affiliation: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
name: Renchi Yang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Nanfang Hospital, Southern Medical University
name: Jing Sun, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Henan Cancer Hospital
name: Hu Zhou, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of USTC (Anhui Provincial Hospital)
name: Changcheng Zheng, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Xiangya Hospital of Central South University
name: Xielan Zhao, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Tai Zhou First People's Hospital
name: Lili Chen, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Jiangxi Provincial People's Hopital
name: Chenghao Jin, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Xi'an Central Hospital
name: Yanping Song, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: LanZhou University
name: Yaming Xi, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Second Affiliated Hospital of Kunming Medical University
name: Zeping Zhou, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Children's Hospital
name: Runhui Wu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Soochow University
name: Ziqiang Yu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: North China University of Science and Technology Affiliated Hospital
name: Zhenyu Yan, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Hospital of Jilin University
name: Sujun Gao, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shengjing Hospital of China University
name: Wei Yang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Third People's Hospital of Chengdu
name: Rong Zhou, Doctor
role: PRINCIPAL_INVESTIGATOR
References: