Clinical trial NCT06399289: Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Chinese Subjects With Hemophilia B Previously Treated With FIX Therapy
Official title: A Phase 3, Open-label, Multicenter, Pharmacokinetics, Efficacy, and Safety Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Previously Treated Chinese Subjects With Hemophilia B
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hemophilia B
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2024-05-03
Enrollment: 23
Sex: MALE
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Incremental recovery (IR) (plasma FIX activity)
timeFrame: Before, and at 30 minutes after the end of, rIX-FP infusion on Day 1
measure: Maximum plasma concentration (Cmax)
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
measure: Terminal elimination half-life (t1/2) of rIX-FP
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
measure: Area under the concentration-time curve (AUC)
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
measure: Clearance (Cl) of rIX-FP
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
measure: Annualized spontaneous bleeding rate (AsBR)
timeFrame: Up to 18 months
measure: Number of subjects who develop an inhibitor to FIX
timeFrame: Up to 18 months after rIX-FP infusion
Secondary outcomes:
measure: Percentage of area under the concentration-time curve extrapolated (%AUCExt)
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
measure: Area under the first moment versus time curve extrapolated to infinity (AUMC0-∞)
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
measure: Mean residence time (MRT)
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
measure: Apparent volume of distribution during the terminal phase (Vz)
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
measure: Apparent volume of distribution at steady-state (Vss)
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
measure: Time to reach Cmax (Tmax)
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
measure: Elimination rate constant (λz)
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
measure: Incremental recovery (IR) (plasma FIX activity) - Repeat PK
timeFrame: Before, and at 30 minutes after the end of, rIX-FP infusion at Week 26
measure: Maximum plasma concentration (Cmax) - Repeat PK
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26
measure: Terminal elimination half-life (t1/2) of rIX-FP - Repeat PK
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26
measure: Area under the concentration-time curve (AUC) - Repeat PK
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26
measure: Clearance (Cl) of rIX-FP - Repeat PK
timeFrame: Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26
measure: Annualized bleeding rate (ABR)
timeFrame: Up to 18 months after rIX-FP infusion
measure: Annualized joint bleeding rate (AjBR)
timeFrame: Up to 18 months after rIX-FP infusion
measure: Clinical evaluation of hemostatic efficacy for major bleeding episodes
timeFrame: Up to 18 months after rIX-FP infusion
measure: Change in target joints
timeFrame: At baseline and up to 18 months after rIX-FP infusion
measure: Consumption of rIX-FP - number of rIX-FP infusions (doses)
timeFrame: Up to 18 months after rIX-FP infusion
measure: Consumption of rIX-FP - IU/kg per subject per month
timeFrame: Up to 18 months after rIX-FP infusion
measure: Consumption of rIX-FP - IU/kg per subject per year
timeFrame: Up to 18 months after rIX-FP infusion
measure: Number of bleeding episodes requiring rIX-FP to achieve hemostasis
timeFrame: Up to 18 months after rIX-FP infusion
measure: Percentage of bleeding episodes requiring rIX-FP to achieve hemostasis
timeFrame: Up to 18 months after rIX-FP infusion
measure: Number of subjects who develop antibodies against rIX-FP
timeFrame: Before, and up to 18 months after, rIX-FP infusion
measure: Number of subjects who develop antibodies against Chinese hamster ovary host cell protein
timeFrame: Before, and up to 18 months after, rIX-FP infusion
measure: The number of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP
timeFrame: Up to 18 months after rIX-FP infusion
measure: The percentage of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP
timeFrame: Up to 18 months after rIX-FP infusion
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Children's Hospital
state: Beijing
city: Fuzhou
country: China
facility: Union Hospital Affiliated to Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Guiyang
country: China
facility: Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Tangshan
country: China
facility: North China University Of Science And Technology Affiliated Hospital
state: Hebei
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Tianjin
country: China
facility: Hospital of Hematology, Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
affiliation: CSL Behring
name: Clinical Program Director
role: STUDY_DIRECTOR
References: