This study will investigate the pharmacokinetics (PK), efficacy, and safety of rIX-FP for the routine prophylaxis of bleeding episodes in male Chinese previously treated patients (PTPs) with hemophilia B (FIX activity of ≤ 2%). In addition to the scheduled rIX-FP prophylaxis regimen, subjects may also receive rIX-FP episodic (on-demand) treatment for breakthrough bleeding episodes and rIX-FP for the prophylaxis and treatment of bleeding in emergency surgical procedures.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
23
Lyophilized powder for solution for intravenous injection
Beijing Children's Hospital
Beijing, Beijing Municipality, China
Union Hospital Affiliated to Fujian Medical University
Fuzhou, Fujian, China
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, China
Affiliated Hospital of Guizhou Medical University
Guiyang, Guizhou, China
North China University Of Science And Technology Affiliated Hospital
Tangshan, Hebei, China
Jinan Central Hospital
Jinan, Shandong, China
Hospital of Hematology, Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, China
Incremental recovery (IR) (plasma FIX activity)
Time frame: Before, and at 30 minutes after the end of, rIX-FP infusion on Day 1
Maximum plasma concentration (Cmax)
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
Terminal elimination half-life (t1/2) of rIX-FP
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
Area under the concentration-time curve (AUC)
AUC from time zero to the last measurable concentration (plasma FIX activity) (AUC0-last), and AUC from time zero extrapolated to infinity (AUC0-inf).
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
Clearance (Cl) of rIX-FP
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
Annualized spontaneous bleeding rate (AsBR)
AsBR for treated bleeding episodes, by prophylaxis regimen and overall
Time frame: Up to 18 months
Number of subjects who develop an inhibitor to FIX
Time frame: Up to 18 months after rIX-FP infusion
Percentage of area under the concentration-time curve extrapolated (%AUCExt)
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
Area under the first moment versus time curve extrapolated to infinity (AUMC0-∞)
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
Mean residence time (MRT)
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
Apparent volume of distribution during the terminal phase (Vz)
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
Apparent volume of distribution at steady-state (Vss)
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
Time to reach Cmax (Tmax)
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
Elimination rate constant (λz)
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
Incremental recovery (IR) (plasma FIX activity) - Repeat PK
Time frame: Before, and at 30 minutes after the end of, rIX-FP infusion at Week 26
Maximum plasma concentration (Cmax) - Repeat PK
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26
Terminal elimination half-life (t1/2) of rIX-FP - Repeat PK
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26
Area under the concentration-time curve (AUC) - Repeat PK
AUC from time zero to the last measurable concentration (plasma FIX activity) (AUC0-last), and AUC from time zero extrapolated to infinity (AUC0-inf).
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26
Clearance (Cl) of rIX-FP - Repeat PK
Time frame: Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26
Annualized bleeding rate (ABR)
ABR for treated, untreated, and both treated and untreated bleeding episodes (spontaneous bleeding, traumatic bleeding, unknown bleeding, and total bleeding episodes), by prophylaxis regimen and overall
Time frame: Up to 18 months after rIX-FP infusion
Annualized joint bleeding rate (AjBR)
AjBR for treated, untreated, and both treated and untreated bleeding episodes, by prophylaxis regimen and overall
Time frame: Up to 18 months after rIX-FP infusion
Clinical evaluation of hemostatic efficacy for major bleeding episodes
The investigator will rate the efficacy of the rIX-FP treatment for major bleeding episodes based on a hemostatic efficacy four point rating scale of "excellent, good, moderate or no efficacy", by prophylaxis regimen and overall
Time frame: Up to 18 months after rIX-FP infusion
Change in target joints
Time frame: At baseline and up to 18 months after rIX-FP infusion
Consumption of rIX-FP - number of rIX-FP infusions (doses)
Consumption of rIX-FP expressed as number of rIX-FP infusions (doses), for the prophylaxis regimens, episodic (on-demand) treatment for bleeding episodes (if any), and total (overall) treatment
Time frame: Up to 18 months after rIX-FP infusion
Consumption of rIX-FP - IU/kg per subject per month
Consumption of rIX-FP expressed as total amount (IU/kg) per subject per month, for the prophylaxis regimens, episodic (on-demand) treatment for bleeding episodes (if any), and total (overall) treatment
Time frame: Up to 18 months after rIX-FP infusion
Consumption of rIX-FP - IU/kg per subject per year
Consumption of rIX-FP expressed as total amount (IU/kg) per subject per year, for the prophylaxis regimens, episodic (on-demand) treatment for bleeding episodes (if any), and total (overall) treatment.
Time frame: Up to 18 months after rIX-FP infusion
Number of bleeding episodes requiring rIX-FP to achieve hemostasis
Number of bleeding episodes requiring 1, ≤ 2, or \> 2 infusions (doses) of rIX-FP to achieve hemostasis
Time frame: Up to 18 months after rIX-FP infusion
Percentage of bleeding episodes requiring rIX-FP to achieve hemostasis
Percentage of bleeding episodes requiring 1, ≤ 2, or \> 2 infusions (doses) of rIX-FP to achieve hemostasis
Time frame: Up to 18 months after rIX-FP infusion
Number of subjects who develop antibodies against rIX-FP
Time frame: Before, and up to 18 months after, rIX-FP infusion
Number of subjects who develop antibodies against Chinese hamster ovary host cell protein
Time frame: Before, and up to 18 months after, rIX-FP infusion
The number of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP
Time frame: Up to 18 months after rIX-FP infusion
The percentage of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP
Time frame: Up to 18 months after rIX-FP infusion
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