Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT06312475

Efficacy and Safety of KN057 Prophylaxis in Patients With Haemophilia 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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

Conditions

Hemophilia A With Inhibitor Hemophilia B With Inhibitor

Age range

12 year–70 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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;
  • 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;
  • ≥6 treated bleeding episodes within 26 weeks before screening;
  • Have not used TFPI antibody drugs before;
  • Be able and agree to elute prior drugs for the treatment of hemophilia.

Exclusion criteria

  • Have serious or poorly controlled chronic diseases or obvious systemic diseases;
  • Have a history of thromboembolic disease, or currently have symptoms or signs related to thromboembolic disease or being treated with thrombolytic/antithrombotic therapy;
  • 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;
  • The presence of other inherited or acquired bleeding disorders other than hemophilia A and hemophilia B;
  • 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);
  • Ongoing or planned Immune Tolerance Induction treatment;
  • When bleeding occurred in the past, rFVIIa was ineffective and PCC treatment must be used;
  • Known or suspected hypersensitivity to any constituent of the trial product or related products;
  • Have undergone major surgery (as determined by the investigator) within 3 months before screening, or have elective surgery planned during the study.

Treatment and study plan

KN057

Drug

KN057 will be administered subcutaneously once a week.

Primary outcomes

  1. Annualized bleeding rate (ABR) calculated based on treated spontaneous and traumatic bleeding episodes in Arm 1 and Arm 2.

    Time frame: From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total

    Treated bleeding refers to the use of bypass agents and/or coagulation factors for hemostatic treatment of the bleeding.

Secondary outcomes

  1. 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.

    Time frame: From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total

    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.

  2. ABR calculated based on bleeding episodes and treated bleeding episodes respectively in Arm 2.

    Time frame: From Day 183 (the beginning of the extension period) to Day 365 (the end of the extension period), approximately 26 weeks in total

    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.

  3. 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.

    Time frame: From Day 1 (the beginning of the main trial) to Day 365 (the end of the extension period), approximately 52 weeks in total

    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.

  4. Change from baseline in Hemophilia Joint Health Score (HJHS) scores in Arm 1 and Arm 2.

    Time frame: From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total

    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.

  5. Change in HJHS scores from baseline in Arm 1 and from the 26th week in Arm 2.

    Time frame: From Day 1 (the beginning of the main trial) to Day 365 (the end of the extension period), approximately 52 weeks in total

    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.

  6. Change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L) in Arm 1 and Arm 2.

    Time frame: From Day 1 (the beginning of the main trial) to Day 183 (the end of the main trial), approximately 26 weeks in total

    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).

  7. Change in EQ-5D-5L from baseline in Arm 1 and from the 26th week in Arm 2.

    Time frame: From Day 1 (the beginning of the main trial) to Day 365 (the end of the extension period), approximately 52 weeks in total

    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).

  8. Incidence of TEAE, TEAE related to the experimental drug and SAE.

    Time frame: 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

    TEAE refers to 'treatment emergent adverse event'. SAE refers to 'serious adverse event'.

  9. Incidence of thromboembolic events, TMA and DIC.

    Time frame: 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

    TMA refers to 'thrombotic microangiopathy'. DIC refers to 'disseminated intravascular coagulation'.

  10. Incidence of hypersensitivity type reactions.

    Time frame: 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

  11. Incidence of injection site reactions.

    Time frame: 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

  12. Incidence of clinically significant laboratory value abnormalities.

    Time frame: 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

  13. Number of participants with clinically significant changes from baseline in physical exam.

    Time frame: 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

  14. Number of participants with clinically significant changes from baseline in electrocardiograms.

    Time frame: 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

  15. Number of participants with clinically significant changes from baseline in vital signs.

    Time frame: 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

  16. KN057 plasma trough concentration.

    Time frame: 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

    pharmacokinetics

  17. Levels of Free TFPI.

    Time frame: 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

    pharmacodynamics

  18. Levels of prothrombin fragment 1+2 (PF1+2).

    Time frame: 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

    pharmacodynamics

  19. Incidence of anti-KN057 antibody (ADA) and neutralizing antibody (Nab).

    Time frame: 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

    immunogenicity

Sponsors and collaborators

Lead sponsor

Suzhou Alphamab Co., Ltd.

Industry

Registry information

Official study 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

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Mar 15, 2024
Registry last updated
Sep 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.