Clinical trial NCT06569108: Efficacy and Safety of KN057 Prophylaxis in Patients With Haemophilia A or B Without 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 Without Inhibitors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hemophilia A Without Inhibitor
Hemophilia B Without Inhibitor
Lead sponsor: Suzhou Alphamab Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-08-23
Enrollment: 111
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 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.


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 ≥30 kg and BMI \<28 kg/m\^2 at screening;
2. Severe and moderately severe hemophilia A or hemophilia B (FVIII or FIX activity level ≤2%);
3. 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;
4. There is no history of FVIII or FIX inhibitors in the past; or there has been an inhibitor, but it has been at least 5 years since successful immune tolerance induction therapy (ITI), and the inhibitor has not reappeared (a positive inhibitor was detected after successful ITI);
5. Use coagulation factor replacement therapy for no less than 100 exposure days before screening;
6. Have not used Anti-TFPI drugs before;
7. Be able and agree to elute the original hemophilia drugs.

Participants who are enrolled into Part A must also meet the following criteria:

1. ≥6 treated bleeding episodes within 26 weeks before screening;
2. Receiving on-demand treatment, non-standard prophylaxis, or standard prophylaxis no more than 12 weeks before screening;

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:

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. Known or suspected hypersensitivity to any constituent of the trial product or related products;
6. Have undergone major surgery (as determined by the investigator) within 3 months before screening, or have elective surgery planned during the study;
7. Used Emicizumab treatment within 6 months before screening;
8. Have received any gene therapy for hemophilia in the past;
9. 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.

Primary outcomes:
measure: Part A: Annualized bleeding rate (ABR) calculated based on treated spontaneous and traumatic bleeding episodes in Experimental group and Control group.
timeFrame: From Week 1 to Week 26, through the main trial.
measure: Part B: ABR calculated based on treated spontaneous and traumatic bleeding episodes in Prophylaxis group.
timeFrame: From Week 1 to Week 26, through the factor period. From Week 27 to Week 52, through the KN057 period.
Secondary outcomes:
measure: 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.
timeFrame: From Week 1 to Week 52, through the main trial and extension period.
measure: 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.
timeFrame: From Week 1 to Week 26. From Week 27 to Week 52.
measure: Proportion of participants with untreated bleeding episodes in Experimental group, Control group and Prophylaxis group.
timeFrame: From Week 1 to Week 26. From Week 27 to Week 52.
measure: The annual usage of on-demand treatment drugs (adjusted by body weight) in Experimental group and Control group.
timeFrame: From Week 1 to Week 26. From Week 27 to Week 52.
measure: Change from baseline in Hemophilia Joint Health Score (HJHS) scores in Experimental group, Control group and Prophylaxis group.
timeFrame: From Week 1 to Week 26.
measure: 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.
timeFrame: From Week 1 to Week 52.
measure: Change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L) in Experimental group, Control group and Prophylaxis group.
timeFrame: From Week 1 to Week 26.
measure: 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.
timeFrame: From Week 1 to Week 52.
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 concentration.
timeFrame: 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.
measure: Levels of Total TFPI.
timeFrame: 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.
measure: Levels of Free TFPI.
timeFrame: 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.
measure: Levels of prothrombin fragment 1+2 (PF1+2).
timeFrame: 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.
measure: Incidence of anti-KN057 antibody (ADA) and neutralizing antibody (Nab).
timeFrame: 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.
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: 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
affiliation: The First Affiliated Hospital of Soochow University
name: Ziqiang Yu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Qianfoshan Hospital
name: Yun Chen, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Henan Provincial People's Hospital
name: Pingchong Lei, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Bao Ji Central Hospital
name: Yinsuo Zheng, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Guangxi Medical University
name: Peng Cheng, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Chongqing Medical University
name: Jianwen Xiao, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Nanchang University
name: Ruibin Huang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The first affiliated hospital of jiangxi medical college
name: Hailiang Li, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Second Affiliated Hospital of Chongqing Medical University
name: Shu Chen, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Maoming City People's Hospital
name: Xiong Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Second Hospital of Hebei Medical Hospital
name: Jingyu Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Shijitan Hospital, Capital Medical University
name: Baolai Hua, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Huai'an Second People'Hospital
name: Yanming Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
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