Hemophilia A/B and congenital deficiency of coagulation factor VII
Conditions
Interventions
Group C: every 8 w
Experimental Group PartA:PartA(Non randomized):This phase utilizes a combined accelerated titration and "3+3" design for dose escalation across six predefined dose cohorts (0.025, 0.05, 0.1, 0.2, 0.4,
Experimental Group PartB:PartB(Non randomized):This phase is a two-dose, open-label, multiple-dose Phase IIa exploratory trial evaluating the efficacy of prophylactic treatment, enrolling 12 subjects
Experimental Group PartC:PartC(Randomized):This phase IIb randomized, open-label, multiple-dose exploratory trial evaluates the prophylactic efficacy of three extended-interval dosing regimens (Group
Group B: every 6 weeks
Sponsors
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: At the time of signing the informed consent form, the age should be between 18 and 65 years old, and both genders should be male. 2. Patients clinically diagnosed with hemophilia A or B or congenital deficiency of coagulation factor VII, and must meet the following conditions: 1) Patients with hemophilia A or B whose F? activity level was =2. 4. Only Part B stage: At least 3 months of bleeding treatment records (factor replacement or bypass drug treatment) before enrollment can be obtained. For patients with hemophilia A or B, on-demand treatment within 3 months before enrollment is available, and the number of new bleeding events after treatment is >=3. For patients with congenital coagulation factor VII deficiency, the number of new bleeding events after treatment within 3 months before enrollment is >=2. 5. There were no symptoms of active bleeding before the first medication. 6. The subject or impartial witness fully understands and can comply with the requirements of the trial protocol, is willing to complete the research as planned, and voluntarily cooperates with the provision of biological samples for testing as required by the protocol; 7. Be able to understand the procedures and methods of this clinical trial. With full informed consent, the patient voluntarily participates and signs the informed consent form by themselves.
Exclusion criteria
Exclusion criteria: Patients who are known to have a history of hypersensitivity reactions to the investigational drug formulation and any of its components; 2. Subcutaneous injection intolerance or the presence of other local skin abnormalities or skin diseases that affect administration and safety assessment; 3. Those who meet one of the following indicators during the screening period: hemoglobin =2.5 times the upper limit of the normal value (ULN), or total bilirubin >=1.5 times ULN; Or those with serum creatinine (Cr) >=1.5 times ULN; Those who test positive for hepatitis B surface antigen (HBsAg), anti-human immunodeficiency virus (HIV) antibody and Treponema pallidum specific antibody in one or more items; 4. Those clinically diagnosed with active hepatitis C; 5. Any other bleeding disorders or other diseases that cause significant abnormalities in coagulation indicators, except for hemophilia A or B and congenital deficiency of coagulation factor VII (such as platelet disorders, vitamin K deficiency, etc.); 6. Suffering from protein C deficiency or protein S deficiency; 7. There is a history of thrombosis or a family history of thrombosis, or a history of thrombophilia before or at present before signing the informed consent form; 8. Those who have suffered from intracranial hemorrhage due to hemophilia A or B and congenital deficiency of coagulation factor VII within the two years prior to screening; 9. Suffering from severe heart diseases, such as unstable angina pectoris, congestive heart failure (New York Heart Association grade = III), severe arrhythmia (QTc interval >450ms, corrected by Fridericia formula), uncontrollable hypertension (systolic blood pressure >= 160 mmHg or diastolic blood pressure >=95 mmHg), etc. 10. Had received recombinant human coagulation factor ?a (rFVIIa) within 48 hours before the first administration; Received any product containing F? within 72 hours before the first administration; Have received any product containing FIX within 96 hours before the first use; The long-acting products of the above-mentioned drugs eluted within less than five half-lives. 11. Those who have used any anticoagulants, antifibrinolytic agents, or chemical drugs, biological products, or traditional Chinese medicines that affect platelet function within one week before the first administration or need to use them during the trial period, including non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, etc. 12. Those who received whole blood or plasma therapy within 2 weeks before the first administration; 13. Those who have received emicizumab treatment within 6 months prior to the first medication; 14. Have received or plan to receive vaccination during the trial period within 4 weeks before the first dose; 15. Those who have undergone major surgical operations (such as orthopedic surgery, abdominal surgery) within one month prior to the first medication, or plan to undergo surgery during the study period; 16. Patients who have been enrolled in other clinical trials within one month prior to the first administration; 17. Patients with a history of drug abuse or alcoholism (Alcoholism criteria: having a long-term drinking history of more than 5 years, equivalent to an alcohol content of >=40g/d for men, or having a history of heavy drinking within 2 weeks, equivalent to an alcoh
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part B/ Part C:Treated total annualized bleeding rate (ABR);part A:Safety and Immunogenicity: Incidence of AEs/SAEs/AESIs assessed through clinical signs and symptoms, vital signs, physical examination, laboratory tests (complete blood count, urinalysis, and blood biochemistry), coagulation function [PT, TT, INR, FIB, APTT, D-dimer], FDP, 12-lead electrocardiogram, injection site reactions, hypersensitivity/allergic reactions, thrombotic events, etc.;;part A:Safety and Immunogenicity:Incidence of drug-related AEs/SAEs/AESIs;part A:Safety and Immunogenicity:Number and incidence of patients with anti-drug antibodies (ADA) and neutralizing antibodies; | — |
Secondary
| Measure | Time frame |
|---|---|
| Part B/ Part C:Treated spontaneous annualized bleeding rate;Part B/ Part C:Treated total annualized joint bleeding rate;Part B/ Part C:Treated annualized menorrhagia bleeding rate (applicable only to reproductive-age female patients with congenital FVII deficiency and active menstruation);Part B/ Part C:Change from baseline in Hemophilia Joint Health Score (HJHS) (for hemophilia A/B patients);Part B/ Part C:Change from baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) score;Part B/ Part C:Multiple-dose pharmacokinetic (PK) parameters: Tmax,ss, Cmax,ss, AUC?–t, CLss/F, Cmin,ss, Cav,ss, AUC?–t,ss, and steady-state fluctuation coefficient (DF), etc. If data permit, t?/?z, AUC?–8, Vz/F, MRT, ?z, and other parameters will be calculated;Part B/ Part C:Safety and Immunogenicity:Incidence of AEs/SAEs/AESIs assessed through clinical signs and symptoms, vital signs, physical examination, laboratory tests (complete blood count, urinalysis, and blood biochemistry), coagulation function [PT, TT, INR, FIB, APTT, D-dimer], FDP, 12-lead electrocardiogram, injection site reactions, hypersensitivity/allergic reactions, thrombotic events, etc.; ;Part B/ Part C:Safety and Immunogenicity:Incidence of drug-related AEs/SAEs/AESIs;Part B/ Part C:Safety and Immunogenicity:Number and incidence of patients with anti-drug antibodies (ADA) and neutralizing antibodies;part A:Single-dose pharmacokinetic (PK) parameters: t?/?z, Cmax, Tmax, AUC?–t, AUC?–8, CLz/F, Vz/F, MRT, etc; | — |
Countries
China
Contacts
Public ContactYang Renchi
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed