Dosage and PD Study of Eftrenonacog-alfa

• Conditions: Severe Haemophilia B
• Interventions: Other: Non interventional study

• Registration Number: NCT04590950
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The purpose of this study is to evaluate the performance of different methods for measuring factor IX activity levels in haemophilia B patients treated with eftrenonacog-alfa and assess its pharmacodynamics (PD) in a real-life setting.

Detailed Description

A recent European survey showed that increasing number of hemophilia B patients was switched from standard to extended half-life drugs. While some clinicians currently prefer to treat empirically rather than based on laboratory results, adoption of replacement therapy based on extended half-life products such as eftrenonacog-alfa may increase the interest in individualized pharmacokinetic assessments allowing the development of an initial dosing regimen. Thus inaccurate FIX activity measurements might be critical, especially when FIX trough level is used to tailor patient dosing regimens. It is therefore important that FIX activity levels are accurately determined allowing adequate recovery without increasing the cost of medical management of hemophilia B patients due to unnecessary dose corrections.

With the expansion of the prescription of eftrenonacog-alfa, the problem of accurately measuring its recovery has risen within hemostasis laboratories. Chronometric one-stage assays (OSA) are currently the most widely performed tests for FIX activity measurement. They are based on activated partial thromboplastin time (aPTT) reagent and factor-deficient plasma. Various aPTT reagents are commercialized. They could lead to a substantial variability in FIX results. Chromogenic two-stage assays (CSA) are less frequently used in clinical laboratories. They present fewer reagent choice compared to OSA. Several studies have evaluated OSA and CSA performances in samples spiked with eftrenonacog-alfa and have evidenced that some commonly used aPTT reagents would not be suitable for accurately monitoring this product. Whether these results are commutable to post-infusion samples collected from real-life patients remains unclear.

Unlike the measurement of a unique coagulation factor activity, thrombin generation assay (TGA) is a dynamic global test that explores the coagulation cascade as well as the anticoagulant pathways. TGA could be therefore a valuable tool to monitor replacement therapy in hemophilia B patients.

Hence the investigators sought in a real-life setting to compare 2 CSA and 1 OSA reagents to a product specific OSA in severe hemophilia B patients supplemented with eftrenonacog-alfa. The investigators also aimed to evaluate the pharmacodynamics (PD) of eftrenonacog-alfa using TGA.

Study Timeline

• Study First Submitted: 2020-07-08
• Status Verified: 2020-08
• Study Start: 2020-10
• Study First Submitted QC: 2020-10-15
• Last Update Submitted: 2020-10-15
• Study First Posted: 2020-10-19
• Last Update Posted: 2020-10-19
• Primary Completion: 2020-12
• Study Completion: 2021-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• severe haemophilia B patients
• treated with eftrenonacog-alfa

Exclusion Criteria

• any other haemostatic or replacement therapy

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Single-group study	Non interventional study	Severe haemophilia B patients substituted with eftrenonacog-alfa

Primary Outcome Measures

Name	Time	Method
FIX activity levels	One month	2 chromogenic assays (Bio phen FIX and Rox FIX) and 2 chronometric assays (CK Prest with standard human plasma or FIX deficient plasma supplemented with eftrenonacog-alfa as calibrators)

Secondary Outcome Measures

Name	Time	Method
Thrombin generation assay	One month	microplate fluorometer, velocity

Trial Locations

Locations (1)

Service d'hématologie biologique - Hôpital Cochin; 🇫🇷 Paris, France