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

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

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 Overview

• Status: Not yet recruiting
• Conditions: Hemophilia B
• Intervention / Treatment: Biological: Recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP)

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Trial Registration Coordinator; Phone Number: 1-610-878-4000; Email: clinicaltrials@cslbehring.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rIX-FP; Subjects will receive rIX-FP as an intravenous (IV) infusion for a minimum of 50 exposure days (EDs)	Biological: Recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP); Lyophilized powder for solution for intravenous injection; Other Names: CSL654; rIX-FP; Idelvion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incremental recovery (IR) (plasma FIX activity)		Before, and at 30 minutes after the end of, rIX-FP infusion on Day 1
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)	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
Clearance (Cl) of rIX-FP		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	Up to 18 months
Number of subjects who develop an inhibitor to FIX		Up to 18 months after rIX-FP infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
Incremental recovery (IR) (plasma FIX activity) - Repeat PK		Before, and at 30 minutes after the end of, rIX-FP infusion at Week 26
Maximum plasma concentration (Cmax) - Repeat PK		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		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).	Before, and up to 336 hours after the end of, rIX-FP infusion at Week 26
Clearance (Cl) of rIX-FP - Repeat PK		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	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	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	Up to 18 months after rIX-FP infusion
Change in target joints		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	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	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.	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	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	Up to 18 months after rIX-FP infusion
Number of subjects who develop antibodies against rIX-FP		Before, and 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
The number of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP		Up to 18 months after rIX-FP infusion
The percentage of subjects with treatment emergent adverse events (TEAEs) related to rIX-FP		Up to 18 months after rIX-FP infusion

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Clinical Program Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 1, 2024
• First Submitted That Met QC Criteria: May 1, 2024
• First Posted (Estimated): May 3, 2024

Study Record Updates

• Last Update Posted (Estimated): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: CSL654_3004; 2022-002333-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available.

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No