KN057 Multiple Dose Study in Moderately Severe to Severe Hemophilia

NCT05421429 | Completed Phase 2

• 1 other identifier: KN057-A-201
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of multiple subcutaneous doses of KN057 in subjects with hemophilia A or B, with or without inhibitors to Factor VIII (FVIII) or Factor IX (FIX). 24 adult participants 18 to 70 years of age with moderately severe to severe hemophilia A or hemophilia B (defined as FVIII or FIX activity ≤2%, respectively) with or without inhibitors (including 18 HA/HB patients without inhibitors and 6 HA/HB patients with inhibitors) are expected to be enrolled in this study during which they will receive prophylaxis treatment (defined as treatment by SC injection once weekly of KN057).

Conditions

Hemophilia

Outcome Measures

Primary Outcomes (10)

• Frequency and severity of treatment emergent adverse events(TEAEs)

  An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (SAE) is any untoward medical occurrence at any dose that resulted in death; life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and non-serious AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment.

  Day 1 up to Day 85

• Withdrawals due to TEAEs

  An AE is any untoward medical occurrence in a clinical investigation participant administered a product and the event does not need to have a causal relationship with the treatment. TEAEs are AEs occurred following the start of treatment or AEs increasing in severity during treatment.

  Day 1 up to Day 85

• Number of Participants With Abnormal Laboratory Findings-Hematology

  White blood cells, red blood cells; the count of lymphocyte, neutrophils, monocytes, eosinophils, basophils; the percentage of lymphocyte, neutrophils, monocytes, eosinophils, basophils; hemoglobin, red blood cell pressure, platelet count

  Day 1 up to Day 85

• Number of Participants With Abnormal Laboratory Findings-Urinalysis

  blood, urobilirubin, urobiliogen, ketone body, protein, nitrite, red blood cell (qualitative and/or quantitative), white blood cell (qualitative and/or quantitative), pH, urinary glucose.

  Day 1 up to Day 85

• Number of Participants With Abnormal Laboratory Findings-Blood biochemistry

  Total bilirubin and indirect bilirubin, direct bilirubin, alanine aminotransferase, aspertate aminotransferase, GGTP (gamma glutamyl transpeptidase), alkaline phosphatase, total protein, albumin, globulin, albumin-globulin ratio, urea, creatinine, uric acid, glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol (ldl-c), high-density lipoprotein cholesterol (hdl-c), lactate dehydrogenase, creatine kinase, chlorine, calcium, sodium, potassium, C reactive protein

  Day 1 up to Day 85

• Number of Participants With Abnormal Laboratory Findings-Coagulation tests

  Prothrombin time (PT), International Standardized ratio (INR), Activated partial thrombin time (APTT), thrombin time (TT), fibrinogen (FBG/FIB), D-dimer (D-DI), fibrinogen degradation product (FDP), antithrombin - ⅲ (AT- ⅲ)

  Day 1 up to Day 85

• Number of Participants With Clinically Significant Changes in Vital Signs Data

  Vital signs：blood pressure (systolic blood pressure, diastolic blood pressure), respiration, temperature, pulse；

  Day 1 up to Day 85

• Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)

  ECG: HR; RR; PR; QRS; QT; QTc

  Day 1 up to Day 85

• Number of Participants With Clinically Significant Changes in Physical Examination Findings

  Physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. Clinical significance was judged by the investigator.

  Day 1 up to Day 85

• Number of Participants With Injection Site Reactions

  Injection site reactions may include, but are not limited to: erythema, sclerosis, ecchymosis, pain, and itching.

  Day 1 up to Day 85

Secondary Outcomes (14)

• Maximum Plasma Concentration (Cmax) of KN057

  Day 1 up to Day 8

• Time to Reach Maximum Plasma Concentration (Tmax) of KN057

  Day 1 up to Day 8

• Area Under the Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of KN057

  Day 1 up to Day 8

• Cmax,ss: Maximum observed KN057 concentration at steady-state

  Day 36 up to Day 43

• Time to Reach Maximum Plasma Concentration at steady-state (Tmax,ss) of KN057

  Day 36 up to Day 43

Study Arms (4)

KN057 (Cohort 1：HA/HB)

EXPERIMENTAL

Injection, once a week

Biological: KN057 doseⅠ

KN057 (Cohort 2：HA/HB)

EXPERIMENTAL

Injection, once a week

Biological: KN057 dose Ⅱ

KN057 (Cohort 3：HA/HB)

EXPERIMENTAL

Injection, once a week

Biological: KN057 dose Ⅱ

KN057 (Cohort 4：HAW/HBW)

EXPERIMENTAL

Injection, once a week

Biological: KN057 dose Ⅲ

Interventions

KN057 doseⅠ BIOLOGICAL

KN057 subcutaneous (SC) injection

KN057 (Cohort 1：HA/HB)

KN057 dose Ⅱ BIOLOGICAL

KN057 SC injection

KN057 (Cohort 2：HA/HB); KN057 (Cohort 3：HA/HB)

KN057 dose Ⅲ BIOLOGICAL

KN057 SC injection

KN057 (Cohort 4：HAW/HBW)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male, 18-70 years old (including threshold), weight≥40kg;
• Moderately severe to severe hemophilia A or B (Factor VIII or Factor IX activity ≤2%)
• Participants who are enrolled into the Non-Inhibitor Cohort must meet the following criteria:
• ①negtive results of of inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in screening period.
• ②with ≥6 acute bleeding episodes (spontaneous or traumatic, not including episodes of bleeding during surgery) that required treatment within 6 months before screening and willing to continue to receive on-demand treatment during the study.
• ③using coagulation factor replacement therapy for more than 50 exposure days before screening.
• Participants who are enrolled into the Inhibitor Cohort must meet the following criteria:
• ①positive results of inhibitors to Factor VIII (FVIII) or Factor IX (FIX) in screening period.
• ②with ≥6 acute bleeding episodes (spontaneous or traumatic, not including episodes of bleeding during surgery) that required treatment within 6 months before screening and willing to continue to receive on-demand treatment during the study.
• Be willing to undergo a washout period of the original treatment regimen before the administration of KN057: at least 48 hours for recombinant activated coagulation factor Ⅶ (rFⅦa); at least 72 hours for FⅧ and prothrombin complex (PCC); at least 96 hours for FⅨ; For other drugs or investigational products with a long half-life, such as Emicizumab, at least five half-lives should have passed prior to dosing.
• Be willing to comply with the relevant management regulations of the clinical trial unit, and follow study procedures.

You may not qualify if:

• Patients with serious or poorly controlled chronic diseases or obvious systemic diseases, such as cardiovascular system, respiratory system, endocrine and metabolic system, urinary system, digestive system, autoimmune diseases, nervous system diseases or psychiatric diseases, bacterial or viral infections, etc.; past or current lipid-lowering treatment for hypertriglyceridemia.
• Inherited or acquired bleeding disorder other than hemophilia A or B.
• Have symptoms or signs related to thromboembolic disease or are receiving thrombolytic/anti-thrombolytic therapy; A history of coronary atherosclerotic diseases, arterial or venous thrombosis, and ischemic diseases of important organs.
• Conditions that may increase risk of thrombosis: including reduced activity of antithrombin III, protein S or protein C;
• Must use PCC to treat acute bleeding episodes, and can't be treated with rFVIIa.
• Ongoing or planned use of immune tolerance induction.
• Regular use of immunomodulatory therapy, such as regular infusion of immunoglobulin or regular use of hormones.
• Allergy situation: Allergic to test drugs/similar drugs or excipients; With a history of multiple allergies (two or more); A history of specific reactions, such as sensitivity to heparin or heparin induced thrombocytopenia.
• Abnormal hematologic parameters: Platelet count≤100×10\^9/L; Hemoglobin \< 100g/L; Fibrinogen level \< LLN; Prothrombin time \> 1.5 times ULN;
• Abnormal renal or hepatic function: Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 3 times ULN; Lactate dehydrogenase (LDH) \> 1.5 times ULN; Total bilirubin (TB) \> 1.5 times ULN; Serum creatinine (Cr) and triglyceride \> ULN; Albumin \< 0.8 times LLN;
• Chronic active hepatitis B/C (HBV-DNA or HCV-RNA quantitative test indicates viral activity); Human immunodeficiency virus (HIV) antibody positive; Syphilis antibody positive; Previous antiviral treatment within 1 month, or a plan for antiviral treatment within 28 weeks of initial administration.
• Had major surgery, as judged by the investigator, within 3 months prior to the study or have elective surgery planned within 28 weeks of initial administration.
• Need to use anti-fibrinolytic drugs or drugs affecting platelet function 5 days before administration or 28 weeks after initial administration, including Traditional Chinese medicine/proprietary Chinese medicine, such as aspirin and other non-steroidal anti-inflammatory drugs, Angelica, astragalus, etc., or proprietary Chinese medicine containing the above ingredients.
• Participated in clinical trials related to coagulation factors within 1 month; Participated in any other drug clinical trials within 3 months.
• Vaccination within 1 month, or within 28 weeks after initial administration, including inactivated vaccines, live attenuated vaccines, recombinant protein vaccines, recombinant adenovirus vaccines, RNA vaccines, DNA vaccines, etc.;

Sponsors & Collaborators

• Suzhou Alphamab Co., Ltd.: lead

Study Sites (2)

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

Tianjin, Tianjin Municipality, 300020, China

Location

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

Tianjin, Tianjin Municipality, 300020, China

Location

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Renchi Yang, Doctor

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

  PRINCIPAL INVESTIGATOR

• Shujie Wang, Doctor

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

• Hu Zhou, Doctor

  Henan Cancer Hospital（The Affiliated Cancer Hospital Of ZhengZhou University)

  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

• Jing Sun, Doctor

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

• Xielan Zhao, Doctor

  Xiangya Hospital of Central South University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2022
• First Posted: June 16, 2022
• Study Start: July 7, 2022
• Primary Completion: January 17, 2024
• Study Completion: January 17, 2024
• Last Updated: December 30, 2024

Record last verified: 2024-09

Locations

CN (2)