Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Chinese Subjects With Hemophilia B Previously Treated With FIX Therapy

Hemophilia B Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06399289
• Other study ID #: CSL654_3004
• Secondary ID: 2022-002333-34
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: December 2026

Study information

• Verified date: May 2024
• Source: CSL Behring
• Contact: Trial Registration Coordinator
• Phone: 1-610-878-4000
• Email: clinicaltrials[@]cslbehring.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 23
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Biological:
• Recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP)
Lyophilized powder for solution for intravenous injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incremental recovery (IR) (plasma FIX activity)		Before, and at 30 minutes after the end of, rIX-FP infusion on Day 1
Primary	Maximum plasma concentration (Cmax)		Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
Primary	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
Primary	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).	Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
Primary	Clearance (Cl) of rIX-FP		Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1
Primary	Annualized spontaneous bleeding rate (AsBR)	AsBR for treated bleeding episodes, by prophylaxis regimen and overall	Up to 18 months
Primary	Number of subjects who develop an inhibitor to FIX		Up to 18 months after rIX-FP infusion
Secondary	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)
Secondary	Area under the first moment versus time curve extrapolated to infinity (AUMC0-8)		Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Elimination rate constant (?z)		Before, and up to 336 hours after the end of, rIX-FP infusion on Day 1 and at Week 26 (Repeat PK)
Secondary	Incremental recovery (IR) (plasma FIX activity) - Repeat PK		Before, and at 30 minutes after the end of, rIX-FP infusion at Week 26
Secondary	Maximum plasma concentration (Cmax) - Repeat PK		Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26
Secondary	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
Secondary	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).	Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26
Secondary	Clearance (Cl) of rIX-FP - Repeat PK		Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26
Secondary	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	Up to 18 months after rIX-FP infusion
Secondary	Annualized joint bleeding rate (AjBR)	AjBR for treated, untreated, and both treated and untreated bleeding episodes, by prophylaxis regimen and overall	Up to 18 months after rIX-FP infusion
Secondary	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	Up to 18 months after rIX-FP infusion
Secondary	Change in target joints		At baseline and up to 18 months after rIX-FP infusion
Secondary	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	Up to 18 months after rIX-FP infusion
Secondary	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	Up to 18 months after rIX-FP infusion
Secondary	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.	Up to 18 months after rIX-FP infusion
Secondary	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	Up to 18 months after rIX-FP infusion
Secondary	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	Up to 18 months after rIX-FP infusion
Secondary	Number of subjects who develop antibodies against rIX-FP		Before, and up to 18 months after, rIX-FP infusion
Secondary	Number of subjects who develop antibodies against Chinese hamster ovary host cell protein		Before, and up to 18 months after, rIX-FP infusion
Secondary	The number of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP		Up to 18 months after rIX-FP infusion
Secondary	The percentage of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP		Up to 18 months after rIX-FP infusion