Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Chinese Subjects With Hemophilia B Previously Treated With FIX Therapy
- Conditions
- Hemophilia B
- Interventions
- Biological: Recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP)
- Registration Number
- NCT06399289
- Lead Sponsor
- CSL Behring
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 23
- Male Chinese subjects aged ≤ 70 years
- Subjects with documented severe or moderately severe hemophilia B (FIX activity of ≤ 2%)
- Subjects have received FIX products for ≥ 150 exposure days (EDs) (subjects aged ≥ 6 years) or ≥ 50 EDs (subjects aged < 6 years)
- Subjects have no confirmed prior history of FIX inhibitor formation
- Known hypersensitivity (allergic reaction or anaphylaxis) to any FIX product or hamster protein.
- Known congenital or acquired coagulation disorder other than congenital FIX deficiency.
- Currently receiving intravenous (IV) immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment.
- Currently receiving a long-acting recombinant FIX treatment such as coagulation factor IX (recombinant), Fc fusion protein (Alprolix®).
- Use of traditional or herbal Chinese medicine(s) with an impact on hemophilia, including coagulation, within 28 days before Day 1 and / or refusal to abstain from these during the study until the end of the subject's participation in the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description rIX-FP Recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) Subjects will receive rIX-FP as an intravenous (IV) infusion for a minimum of 50 exposure days (EDs)
- Primary Outcome Measures
Name Time Method Number of subjects who develop an inhibitor to FIX Up to 18 months after rIX-FP infusion Maximum plasma concentration (Cmax) 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 Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 Area under the concentration-time curve (AUC) Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 AUC from time zero to the last measurable concentration (plasma FIX activity) (AUC0-last), and AUC from time zero extrapolated to infinity (AUC0-inf).
Clearance (Cl) of rIX-FP Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 Incremental recovery (IR) (plasma FIX activity) Before, and at 30 minutes after the end of, rIX-FP infusion on Day 1 Annualized spontaneous bleeding rate (AsBR) Up to 18 months AsBR for treated bleeding episodes, by prophylaxis regimen and overall
- Secondary Outcome Measures
Name Time Method Change in target joints At baseline and up to 18 months after rIX-FP infusion Consumption of rIX-FP - IU/kg per subject per year Up to 18 months after rIX-FP infusion 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.
Area under the first moment versus time curve extrapolated to infinity (AUMC0-∞) 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) Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK) Annualized joint bleeding rate (AjBR) Up to 18 months after rIX-FP infusion AjBR for treated, untreated, and both treated and untreated bleeding episodes, by prophylaxis regimen and overall
Apparent volume of distribution during the terminal phase (Vz) 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 Before, and at 30 minutes after the end of, rIX-FP infusion at Week 26 Consumption of rIX-FP - number of rIX-FP infusions (doses) Up to 18 months after rIX-FP infusion 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 to reach Cmax (Tmax) Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK) Maximum plasma concentration (Cmax) - Repeat PK Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26 Clinical evaluation of hemostatic efficacy for major bleeding episodes Up to 18 months after rIX-FP infusion 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
Apparent volume of distribution at steady-state (Vss) 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) 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 concentration-time curve (AUC) - Repeat PK Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26 AUC from time zero to the last measurable concentration (plasma FIX activity) (AUC0-last), and AUC from time zero extrapolated to infinity (AUC0-inf).
Clearance (Cl) of rIX-FP - Repeat PK Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26 Percentage of bleeding episodes requiring rIX-FP to achieve hemostasis Up to 18 months after rIX-FP infusion Percentage of bleeding episodes requiring 1, ≤ 2, or \> 2 infusions (doses) of rIX-FP to achieve hemostasis
Percentage of area under the concentration-time curve extrapolated (%AUCExt) Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK) Terminal elimination half-life (t1/2) of rIX-FP - Repeat PK Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26 Number of bleeding episodes requiring rIX-FP to achieve hemostasis Up to 18 months after rIX-FP infusion Number of bleeding episodes requiring 1, ≤ 2, or \> 2 infusions (doses) of rIX-FP to achieve hemostasis
Number of subjects who develop antibodies against rIX-FP Before, and up to 18 months after, rIX-FP infusion The number of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP Up to 18 months after rIX-FP infusion Annualized bleeding rate (ABR) Up to 18 months after rIX-FP infusion 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
Consumption of rIX-FP - IU/kg per subject per month Up to 18 months after rIX-FP infusion 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
The percentage of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP Up to 18 months after rIX-FP infusion Number of subjects who develop antibodies against Chinese hamster ovary host cell protein Before, and up to 18 months after, rIX-FP infusion
Trial Locations
- Locations (7)
Beijing Children's Hospital
🇨🇳Beijing, Beijing, 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, China