Efficacy and Safety of KN057 Prophylaxis in Patients With Haemophilia A or B With Inhibitors

A Randomized, Open-label Study to Evaluate the Efficacy and Safety of KN057 Injection Prophylaxis in Patients With Hemophilia A or B With Inhibitors

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hemophilia A With Inhibitor; Hemophilia B With Inhibitor
• Intervention / Treatment: Drug: KN057

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: KN057 Prophylaxis; Successfully screened participants will be randomly assigned to KN057 Prophylaxis versus No Prophylaxis at a ratio of 2:1. Participants in Arm 1 (KN057 Prophylaxis) will receive KN057 through the main trial (26 weeks) and extension period (26 weeks) for total of approximately 1 year.	Drug: KN057; KN057 will be administered subcutaneously once a week.
Experimental: Arm 2: No Prophylaxis; Successfully screened participants will be randomly assigned to KN057 Prophylaxis versus No Prophylaxis at a ratio of 2:1. Participants in Arm 2 (No Prophylaxis) will continue on-demand treatment with their usual bypass agents (rFVIIa or PCC) through the main trial for 26 weeks, in the extension period they will switch to prophylaxis treatment and receive KN057 for 26 weeks.	Drug: KN057; KN057 will be administered subcutaneously once a week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized bleeding rate (ABR) calculated based on treated spontaneous and traumatic bleeding episodes in Arm 1 and Arm 2.	Treated bleeding refers to the use of bypass agents and/or coagulation factors for hemostatic treatment of the bleeding.	From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Bleeding episodes includes spontaneous and/or traumatic bleeding episodes, excluding surgery/procedure-related bleeding episodes. Treated bleeding refers to the use of bypass agents and/or coagulation factors for hemostatic treatment of the bleeding. Target joint are those with spontaneous bleeding ≥3 times in the 6 months prior to screening.	From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total
ABR calculated based on bleeding episodes and treated bleeding episodes respectively in Arm 2.	Bleeding episodes includes spontaneous and/or traumatic bleeding episodes, excluding surgery/procedure-related bleeding episodes. Treated bleeding refers to the use of bypass agents and/or coagulation factors for hemostatic treatment of the bleeding.	From Day 183 (the beginning of the extension period) to Day 365 (the end of the extension period), approximately 26 weeks in total
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.	Bleeding episodes includes spontaneous and/or traumatic bleeding episodes, excluding surgery/procedure-related bleeding episodes. Treated bleeding refers to the use of bypass agents and/or coagulation factors for hemostatic treatment of the bleeding. Target joint are those with spontaneous bleeding ≥3 times in the 6 months prior to screening.	From Day 1 (the beginning of the main trial) to Day 365 (the end of the extension period), approximately 52 weeks in total
Change from baseline in Hemophilia Joint Health Score (HJHS) scores in Arm 1 and Arm 2.	Hemophilia Joint Health Scores (HJHS) is a validated 11-item scoring tool developed for the assessment of joint health in participants with hemophilia. It comprised an evaluation of the elbows, knee and ankle joints: swelling (0 to 3), duration of swelling (0 and 1), muscle atrophy (0 to 2), crepitus on motion (0 to 2), flexion loss (0 to 3), extension loss (0 to 3), joint pain (0 to 2) and strength (0 to 4), in each item 0 = none and higher score = severe damage and global gait (walking, stairs, running, hopping on 1 leg) scored on scale ranged from 0 to 4, where 0 = all skills in normal limit and 4 = no skills within normal limits). Total HJHS score = sum of joint totals (0 to 120) + general gait (1 to 4) and ranged from 0 (no joint damage) to 124 (severe joint damage), where higher score indicated severe joint damage.	From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total
Change in HJHS scores from baseline in Arm 1 and from the 26th week in Arm 2.	Hemophilia Joint Health Scores (HJHS) is a validated 11-item scoring tool developed for the assessment of joint health in participants with hemophilia. It comprised an evaluation of the elbows, knee and ankle joints: swelling (0 to 3), duration of swelling (0 and 1), muscle atrophy (0 to 2), crepitus on motion (0 to 2), flexion loss (0 to 3), extension loss (0 to 3), joint pain (0 to 2) and strength (0 to 4), in each item 0 = none and higher score = severe damage and global gait (walking, stairs, running, hopping on 1 leg) scored on scale ranged from 0 to 4, where 0 = all skills in normal limit and 4 = no skills within normal limits). Total HJHS score = sum of joint totals (0 to 120) + general gait (1 to 4) and ranged from 0 (no joint damage) to 124 (severe joint damage), where higher score indicated severe joint damage.	From Day 1 (the beginning of the main trial) to Day 365 (the end of the extension period), approximately 52 weeks in total
Change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L) in Arm 1 and Arm 2.	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).	From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total
Change in EQ-5D-5L from baseline in Arm 1 and from the 26th week in Arm 2.	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).	From Day 1 (the beginning of the main trial) to Day 365 (the end of the extension period), approximately 52 weeks in total
Incidence of TEAE, TEAE related to the experimental drug and SAE.	TEAE refers to 'treatment emergent adverse event'. SAE refers to 'serious adverse event'.	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
Incidence of thromboembolic events, TMA and DIC.	TMA refers to 'thrombotic microangiopathy'. DIC refers to 'disseminated intravascular coagulation'.	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
Incidence of hypersensitivity type reactions.		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
Incidence of injection site reactions.		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
Incidence of clinically significant laboratory value abnormalities.		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
Number of participants with clinically significant changes from baseline in physical exam.		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
Number of participants with clinically significant changes from baseline in electrocardiograms.		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
Number of participants with clinically significant changes from baseline in vital signs.		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
KN057 plasma trough concentration.	pharmacokinetics	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
Levels of Free TFPI.	pharmacodynamics	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
Levels of prothrombin fragment 1+2 (PF1+2).	pharmacodynamics	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
Incidence of anti-KN057 antibody (ADA) and neutralizing antibody (Nab).	immunogenicity	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

Collaborators and Investigators

• Sponsor: Suzhou Alphamab Co., Ltd.
• Investigators: Principal Investigator: Renchi Yang, Doctor, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences; Principal Investigator: Ziqiang Yu, Doctor, The First Affiliated Hospital of Soochow University; Principal Investigator: Changcheng Zheng, Doctor, The First Affiliated Hospital of USTC (Anhui Provincial Hospital); Principal Investigator: Xielan Zhao, Doctor, Xiangya Hospital of Central South University; Principal Investigator: Jing Sun, Doctor, Nanfang Hospital, Southern Medical University; Principal Investigator: Hu Zhou, Doctor, Henan Cancer Hospital; Principal Investigator: Lili Chen, Doctor, Tai Zhou First People's Hospital; Principal Investigator: Chenghao Jin, Doctor, Jiangxi Provincial People's Hopital; Principal Investigator: Yanping Song, Doctor, Xi'an Central Hospital; Principal Investigator: Yaming Xi, Doctor, LanZhou University; Principal Investigator: Zeping Zhou, Doctor, The Second Affiliated Hospital of Kunming Medical University; Principal Investigator: Runhui Wu, Doctor, Beijing Children's Hospital; Principal Investigator: Sujun Gao, Doctor, The First Hospital of Jilin University; Principal Investigator: Wei Yang, Doctor, Shengjing Hospital of China University; Principal Investigator: Rong Zhou, Doctor, The Third People's Hospital of Chengdu; Principal Investigator: Jingyu Yan, Doctor, North China University of Science and Technology Affiliated Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2024
• Primary Completion (Estimated): October 15, 2025
• Study Completion (Estimated): December 15, 2025

Study Registration Dates

• First Submitted: December 30, 2023
• First Submitted That Met QC Criteria: March 8, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: KN057-A-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No