Safety of KN057 Prophylaxis in Patients With Haemophilia A or B

An Open-label Study to Evaluate the Safety of KN057 Long-term Prophylaxis in Patients With Hemophilia A or Hemophilia B With or Without Inhibitors

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.

Study Overview

• Status: Recruiting
• Conditions: Hemophilia A or B
• Intervention / Treatment: Drug: KN057

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yanrong Dong, Master; Phone Number: +86 18914005458; Email: yanrongdong@alphamab.com

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Recruiting
      • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
      • Contact: Renchi Yang, Doctor

Participation Criteria

Eligibility Criteria

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

Description

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.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part PK # Old process Group; 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.	Drug: KN057; KN057 will be administered subcutaneously once a week.
Experimental: Part PK # New process Group; The participants in New process Group will receive new process KN057 prophylaxis for both the first 26 weeks and the last 26 weeks.	Drug: KN057; KN057 will be administered subcutaneously once a week.
Experimental: Part non-PK; The participants in Part non-PK will be treated with new process KN057 for 52 weeks prophylaxis after enrollment.	Drug: KN057; KN057 will be administered subcutaneously once a week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of TEAE.	TEAE refers to 'treatment emergent adverse event'.	Up to 12/26/56 weeks.
Incidence of TEAE related to the experimental drug.		Up to 12/26/56 weeks.
Incidence of SAE.	SAE refers to 'serious adverse event'.	Up to 12/26/56 weeks.
Incidence of thromboembolic events.		Up to 12/26/56 weeks.
Incidence of TMA and DIC.	TMA refers to 'thrombotic microangiopathy'. DIC refers to 'disseminated intravascular coagulation'.	Up to 12/26/56 weeks.
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	immunogenicity	Up to 12/26/56 weeks.
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.	pharmacodynamics	Up to 12/26/56 weeks.
Change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L).	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).	Up to 26/52 weeks.
The annual usage of on-demand treatment drugs (adjusted by body weight).		Up to 26/52 weeks.

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: Changcheng Zheng, Doctor, The First Affiliated Hospital of USTC (Anhui Provincial Hospital); Principal Investigator: Hu Zhou, Doctor, Henan Cancer Hospital; Principal Investigator: Yanping Song, Doctor, Xi'an Central Hospital; Principal Investigator: Zeping Zhou, Doctor, The Second Affiliated Hospital of Kunming Medical University; Principal Investigator: Yinsuo Zheng, Doctor, Bao Ji Central Hospital; Principal Investigator: Shu Chen, Doctor, The Second Affiliated Hospital of Chongqing Medical University; Principal Investigator: Yanming Zhang, Doctor, Huai'an Second People'Hospital; Principal Investigator: Xielan Zhao, Xiangya Hospital of Central South University; Principal Investigator: Hongbo Cheng, Doctor, Jiangxi Provincial People's Hopital; Principal Investigator: Jie Yin, Doctor, the First Affiliated Hospital of Soochow University; Principal Investigator: Zhenyu Yan, Doctor, North China University of Science and Technology; Principal Investigator: Yun Chen, Doctor, Jinan Central Hospital; Principal Investigator: Ying Dong, Doctor, Maoming City People's Hospital; Principal Investigator: Xiaoli Wu, Doctor, The Second Hospital of Hebei Medical Hospital; Principal Investigator: Miaoyong Zhu, Doctor, Wenzhou People's Hospital; Principal Investigator: Haiping Yang, Doctor, The First Affiliated Hospital of Henan University of Science and Technology; Principal Investigator: Qingyi Wang, Doctor, The Fifth Affiliated Hospital of Anhui Medical; Principal Investigator: Wenqian Li, Doctor, Qinghai People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): March 30, 2028

Study Registration Dates

• First Submitted: March 8, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A
• Other Study ID Numbers: KN057-A-303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No