Safety of KN057 Prophylaxis in Patients With Haemophilia A or B

Official title

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

Overview

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.

Interventions

• Drug KN057
  KN057 will be administered subcutaneously once a week.

Primary outcome measures

• Incidence of TEAE. [Time frame: Up to 12/26/56 weeks.]
• Incidence of TEAE related to the experimental drug. [Time frame: Up to 12/26/56 weeks.]
• Incidence of SAE. [Time frame: Up to 12/26/56 weeks.]
• Incidence of thromboembolic events. [Time frame: Up to 12/26/56 weeks.]
• Incidence of TMA and DIC. [Time frame: Up to 12/26/56 weeks.]
• Incidence of hypersensitivity type reactions. [Time frame: Up 12/26/56 weeks.]
• Incidence of injection site reactions. [Time frame: Up to 12/26/56 weeks.]
• Incidence of clinically significant laboratory value abnormalities. [Time frame: Up to 12/26/56 weeks.]
• Number of participants with clinically significant changes from baseline in electrocardiograms. [Time frame: Up to 12/26/56 weeks.]
• Number of participants with clinically significant changes from baseline in vital signs. [Time frame: Up to 12/26/56 weeks.]

Secondary outcome measures (10)

• The exposure levels of KN057 after the first administration in both the new and old processes. [Time frame: Up to 12 weeks.]
• The steady-state trough concentrations of KN057 after the first administration in both the new and old processes. [Time frame: Up to 12 weeks.]
• Incidence of anti-KN057 antibody (ADA) and neutralizing antibody (Nab). [Time frame: Up to 12/26/56 weeks.]
• Annualized bleeding rate (ABR) calculated based on treated spontaneous and traumatic bleeding episodes. [Time frame: Up to 26/52 weeks.]
• ABR calculated based on bleeding episodes, treated spontaneous bleeding episodes, treated joint bleeding episodes. [Time frame: 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. [Time frame: 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. [Time frame: Up to 26 weeks.]
• Levels of Free TFPI. [Time frame: Up to 12/26/56 weeks.]
• Change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L). [Time frame: Up to 26/52 weeks.]
• The annual usage of on-demand treatment drugs (adjusted by body weight). [Time frame: Up to 26/52 weeks.]

Eligibility criteria

Inclusion criteria

• 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.
• 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.

• 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

• 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 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.
• 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.
• Used Emicizumab treatment within 6 months before screening.
• Have received any gene therapy for hemophilia in the past.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

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

Identifiers

NCT: NCT07545395 · KN057-A-303

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗