Brief Title
KN057 Multiple Dose Study in Moderately Severe to Severe Hemophilia
Official Title
An Open, Multicenter, Dose Escalation Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Subcutaneous (SC) Doses of KN057 in Subjects With Hemophilia A or B, With or Without Inhibitors
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).
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Frequency and severity of treatment emergent adverse events(TEAEs)
Secondary Outcome
Maximum Plasma Concentration (Cmax) of KN057
Condition
Hemophilia
Intervention
KN057 doseⅠ
Study Arms / Comparison Groups
KN057 (Cohort 1：HA/HB)
Description: Injection, once a week
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
24
Start Date
June 30, 2022
Completion Date
December 31, 2023
Primary Completion Date
June 30, 2023
Eligibility Criteria
Inclusion Criteria:
1. Male, 18-70 years old (including threshold), weight≥40kg;
2. Moderately severe to severe hemophilia A or B (Factor VIII or Factor IX activity ≤2%)
3. 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.
4. 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.
5. 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.
6. Be willing to comply with the relevant management regulations of the clinical trial
unit, and follow study procedures.
Exclusion Criteria:
1. 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.
2. Inherited or acquired bleeding disorder other than hemophilia A or B.
3. 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.
4. Conditions that may increase risk of thrombosis: including reduced activity of
antithrombin III, protein S or protein C;
5. Must use PCC to treat acute bleeding episodes, and can't be treated with rFVIIa.
6. Ongoing or planned use of immune tolerance induction.
7. Regular use of immunomodulatory therapy, such as regular infusion of immunoglobulin or
regular use of hormones.
8. 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.
9. Abnormal hematologic parameters: Platelet count≤100×10^9/L; Hemoglobin < 100g/L;
Fibrinogen level < LLN; Prothrombin time > 1.5 times ULN;
10. 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;
11. 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.
12. 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.
13. 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.
14. Participated in clinical trials related to coagulation factors within 1 month;
Participated in any other drug clinical trials within 3 months.
15. 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.;
16. Subjects with fertile partners are not willing to use effective contraception during
the study period and for 3 months after the last dosing; Effective contraceptive
methods include: vasectomy, adhere to the scientific use of male condoms, etc.
17. Other factors that the investigator considers unacceptable for participation in the
study.
Gender
Male
Ages
18 Years - 70 Years
Accepts Healthy Volunteers
No
Contacts
Renchi Yang, Doctor, +86 18914005458, [email protected]
Administrative Informations
NCT ID
NCT05421429
Organization ID
KN057-A-201
Responsible Party
Sponsor
Study Sponsor
Suzhou Alphamab Co., Ltd.
Study Sponsor
Renchi Yang, Doctor, Principal Investigator, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Verification Date
June 2022