KN057 Multiple Dose Study in Moderately Severe to Severe Hemophilia
Recruiting
Study Details
Medical Condition
- Hemophilia
Study Drug
- Biological: KN057 doseⅠ
- Biological: KN057 dose Ⅱ
- Biological: KN057 dose Ⅲ
Date
Jul 2022 - Feb 2024
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Male
Age: 18 - 70 Years years
Requirements Information
Inclusion and Exclusion Criteria
Inclusion Criteria
- Inclusion Criteria:
- 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.
- Exclusion Criteria:
- 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.;
- 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.
- Other factors that the investigator considers unacceptable for participation in the study.
Protocol Summary
This study is looking at how safe it is to switch from emicizumab to Mim8, in people with haemophilia A. Mim8 is a new medicine that is used to prevent bleeding episodes in people with haemophilia A. Mim8 works by replacing the function of the missing clotting factor VIII (FVIII). Mim8 will be injected under the skin using a pen-injector either once every week, once every two weeks or once every month. The participants will be trained in using the pen injector. The participants can choose themselves, in collaboration with the study doctor how often they get Mim8 in this study. When the participant will get their first Mim8 injection depends on their current treatment with emicizumab. The participants will get their first Mim8 injection at Visit 2. Participants will have between 6 and 27 Mim8 injections. The total number of injections participants will have depends on their dosing frequency. The study will last for about 6-12 months. While taking part in this study, there are some restrictions about what medicine participant can use. The study doctor will tell the participants more about this. In case the participants experience bleeds, these can be treated with additional haemostatic medicine as agreed with the study doctor. Female participants cannot take part if they are pregnant, breast-feeding or plan to get pregnant during the study period.
Trial Locations
Location
Status
Location
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Tianjin, Tianjin, China, 300020
Status
Recruiting
Location
stitute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Tianjin, Tianjin, China, 300020
Status
Recruiting