A phase I/III, multicenter, prospective, open-label, self-controlled study to evaluate the pharmacokinetics (phase I part), efficacy and safety (phase III part) of freeze-dried human blood-coagulation factor X concentrate (KD-416) in patients with congenital factor X deficiency.
KD-416 Phase I/III Study
Shinmura Yasuhiko
KM Biologics Co., Ltd.
1314-1 Kyokushi Kawabe, Kikuchi-shi, Kumamoto, Japan
+81-968-37-4073
rinkai-jrct@kmbiologics.com
Yamashita Masatoshi
KM Biologics Co., Ltd.
1314-1 Kyokushi Kawabe, Kikuchi-shi, Kumamoto, Japan
+81-968-37-4073
rinkai-jrct@kmbiologics.com
Pending
Aug. 31, 2024
10
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
(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
(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
No limit
No limit
Both
Congenital factor X deficiency
[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 50 IU per kg body weight, and that for adolescents/adults (>=12 years of age)is 40 IU per kg body weight.
KD-416 is slowly administered intravenously below 5 mL per minute.
[Phase III Part]
One vial of KD-416 is reconstituted with 2.5 mL of the attached water for injection.
-On-demand treatment to control bleeding episodes
The dosage for children (<12 years of age)is 30-50 IU per kg body weight (If the baseline FX level is >=40%, the patient receives 30 IU) and that for adolescents/adults (>=12 years of age)is 25-40 IU (If the baseline FX level is >=40%, the patient receives 25 IU) depending on the extent of bleeding.
Multiple administration is allowed at >=24-hour intervals until hemostasis is achieved. The second and the subsequent dosage should be 30 IU for patients <12 years of age and 25 IU for patients >=12 years of age.
-Perioperative management
The dosage before surgery for children (<12 years of age) is 30-50 IU per kg body weight and that for adolescents/adults (>=12 years of age) is 25-40 IU based on the risk of bleeding from invasive procedures. Multiple administration is allowed at >=24-hour intervals until hemostasis is achieved. The second and the subsequent dosage should be 30 IU for patients <12 years of age and 25 IU for patients >=12 years of age.
-Routine prophylaxis
The dosage for children (<12 years of age) is 30-50 IU per kg body weight and that for adolescents/adults (>=12 years of age) is 25-40 IU at intervals of 3-4 days (i.e. 72-96 hours) depending on the extent of bleeding. KD-416 is slowly administered intravenously below 5 mL per minute.
(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
