Congenital factor X deficiency
Conditions
Interventions
[Phase I Part]
One vial of KD-416 is reconstituted with 2.5 mL of the attached water for injection.
The dosage for children (=12 years of age) is 40 IU per kg body weight.
KD-416 is slowly administer
Sponsors
Yamamoto Akihiko
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1)Patients who have provided written informed consent (For patients under18 years of age, legally acceptable representatives have provided written informed consent) (2)Patients with congenital factor X deficiency who require routine prophylaxis and/or on-demand treatment to control bleeding episodes/perioperative management of bleeding (3)[Routine prophylaxis cohort] Patients receiving routine treatments with fresh frozen plasma (FFP), prothrombin complex concentrate (PPC), etc. to control the bleeding tendency (4)[On-demand treatment cohort] Patients who experienced bleeding or excessive menstruation which required treatments with FFPs, PCC, etc. to control bleeding episodes at least once within six months before screening
Exclusion criteria
Exclusion criteria: (1)Patients with inhibitors to human blood-coagulation factor X (FX) or with a history of detectable FX inhibitors (>0.6 BU/mL) (2)Patients with known or suspected coagulation/fibrinolysis defects other than the target disease in this study (3)Patients with a history of disseminated intravascular coagulation or thrombus/embolism (4)Patients with known or suspected hypercoagulation (5)Patients with thrombocytopenia (6)Patients with severe liver disorder or renal disorder -Patients undergoing treatments for severe liver disorder (AST and/or ALT: more than five times the maximum limit in the reference range), hepatic cirrhosis, or hepatic cancer -Patients with severe renal disorder (serum creatinine: more than three times the maximum limit in the reference range) (7)Patients with a severe disease such as a malignant tumor or leukemia which requires or may require chemotherapy or radiotherapy during the study (8)Patients with a history of shock or hypersensitivity to therapeutic proteins including blood products (9)Patients with a history of surgical procedures and who have not completely recovered (10)Patients with disorders or symptoms which investigators considered to disrupt study participation, pose risks to patients or have confounding effects on study observations (11)Patients who had participated in a clinical trial and received other investigational drugs/investigational devices within 30 days before screening or who plan to participate in other clinical trials and receive other investigational drugs/investigational devices during this study (12)Breastfeeding women, pregnant women, women/men planning to have a child, women of childbearing potential who experience menstruation and are premenopausal with no intention to use effective contraceptive devices during this study, and men who are not willing to use effective contraceptive devices during this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| (1)Phase I Part Plasma half-life, maximum plasma concentration (Cmax), time to reach maximum plasma concentration (Tmax), area under the blood concentration-time curve (AUC), volume of distribution (Vd), clearance (CL), elimination rate constant and mean residence time (MRT)* calculated based on the FX level after the initial dose of KD-416 *For both patients aged >=12 and <12, pre-dose FX:C and post-dose FX:Cs (10 minutes, 2 hours, 24 hours, 48 hours, 96 hours and 144 hours after the initial dose) are measured in the central laboratory, and the geometric means are calculated. In case the number of patients aged <12 is not sufficient, the geometric means are used as reference values. (2) Phase III Part Control of bleeding episodes: hemostatic efficacy to resolve a bleed Perioperative management: bleeding control and hemostatic efficacy to resolve a bleed in the perioperative period Routine prophylaxis: annualized bleeding rates (ABR) in the current treatment period and the routine prophylaxis period *ABR = (The number of bleeding episodes during the evaluation period) / (duration of the evaluation period) x 365.25 | — |
Secondary
| Measure | Time frame |
|---|---|
| Following endpoints are assessed. -Pharmacodynamics (PD) during the phase I part -Blood coagulation tests after the initial and fourth doses during phase III part with routine prophylaxis -Blood coagulation tests every four weeks during phase III part with routine prophylaxis -Blood coagulation tests during phase III part with on-demand treatment -Blood coagulation tests during phase III part with perioperative management -Scores of Pictorial Blood Loss Assessment Chart (PBAC) during the current treatment period and phase III part -Descriptive statistics of the duration from bleeding to hemostasis for bleeding episodes requiring hemostatic treatment with each subject's medication -ABR of bleeding episodes not requiring hemostatic treatment with drugs during the current treatment period and during the routine prophylaxis period in the phase III part -ABR of all bleeding episodes during the current treatment period and during the routine prophylaxis period in the phase III part - ABR of bleeding episodes requiring hemostatic treatment with clotting factor concentrates during the current treatment period and during the routine prophylaxis period in the phase III part -Overall efficacy rate by treatment purpose | — |
Contacts
Public ContactMasatoshi Yamashita
KM Biologics Co., Ltd.
Outcome results
None listed