Dosage and PD Study of Eftrenonacog-alfa

NCT ID: NCT04590950

Last Updated: 2025-09-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

15 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-12-18

Study Completion Date

2020-03-31

Brief Summary

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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

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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.

Conditions

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Severe Haemophilia B

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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Single-group study

Severe haemophilia B patients substituted with eftrenonacog-alfa

Non interventional study

Intervention Type OTHER

Non interventional study

Interventions

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Non interventional study

Non interventional study

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* severe haemophilia B patients
* treated with eftrenonacog-alfa

Exclusion Criteria

* any other haemostatic or replacement therapy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Service d'hématologie biologique - Hôpital Cochin

Paris, , France

Site Status

Countries

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France

References

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Peyvandi F, Garagiola I, Boscarino M, Ryan A, Hermans C, Makris M. Real-life experience in switching to new extended half-life products at European haemophilia centres. Haemophilia. 2019 Nov;25(6):946-952. doi: 10.1111/hae.13834. Epub 2019 Aug 16.

Reference Type BACKGROUND
PMID: 31418967 (View on PubMed)

Sommer JM, Buyue Y, Bardan S, Peters RT, Jiang H, Kamphaus GD, Gray E, Pierce GF. Comparative field study: impact of laboratory assay variability on the assessment of recombinant factor IX Fc fusion protein (rFIXFc) activity. Thromb Haemost. 2014 Nov;112(5):932-40. doi: 10.1160/TH13-11-0971. Epub 2014 Aug 21.

Reference Type BACKGROUND
PMID: 25144892 (View on PubMed)

Kitchen S, Tiefenbacher S, Gosselin R. Factor Activity Assays for Monitoring Extended Half-Life FVIII and Factor IX Replacement Therapies. Semin Thromb Hemost. 2017 Apr;43(3):331-337. doi: 10.1055/s-0037-1598058. Epub 2017 Mar 6.

Reference Type BACKGROUND
PMID: 28264199 (View on PubMed)

Dargaud Y, Beguin S, Lienhart A, Al Dieri R, Trzeciak C, Bordet JC, Hemker HC, Negrier C. Evaluation of thrombin generating capacity in plasma from patients with haemophilia A and B. Thromb Haemost. 2005 Mar;93(3):475-80. doi: 10.1160/TH04-10-0706.

Reference Type BACKGROUND
PMID: 15735797 (View on PubMed)

Bowyer AE, Shepherd MF, Kitchen S, Maclean RM, Makris M. Measurement of extended half-life recombinant factor IX products in clinical practice. Int J Lab Hematol. 2019 Apr;41(2):e46-e49. doi: 10.1111/ijlh.12953. Epub 2018 Dec 7. No abstract available.

Reference Type BACKGROUND
PMID: 30536630 (View on PubMed)

Collins PW, Fischer K, Morfini M, Blanchette VS, Bjorkman S; International Prophylaxis Study Group Pharmacokinetics Expert Working Group. Implications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophilia. Haemophilia. 2011 Jan;17(1):2-10. doi: 10.1111/j.1365-2516.2010.02370.x. Epub 2010 Aug 22.

Reference Type BACKGROUND
PMID: 20731726 (View on PubMed)

Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, Ludlam CA, Mahlangu JN, Mulder K, Poon MC, Street A; Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia. Guidelines for the management of hemophilia. Haemophilia. 2013 Jan;19(1):e1-47. doi: 10.1111/j.1365-2516.2012.02909.x. Epub 2012 Jul 6.

Reference Type BACKGROUND
PMID: 22776238 (View on PubMed)

Atsou S, Furlan F, Duchemin J, Ellouze S, Sourdeau E, Launois A, Roussel-Robert V, Stieltjes N, Combe S, Fontenay M, Curis E, Jourdi G. Pharmacodynamics of eftrenonacog-alfa (rFIX-Fc) in severe hemophilia B patients: A real-life study. Eur J Pharmacol. 2021 Jan 15;891:173764. doi: 10.1016/j.ejphar.2020.173764. Epub 2020 Nov 27.

Reference Type BACKGROUND
PMID: 33249076 (View on PubMed)

Other Identifiers

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APHP191124

Identifier Type: -

Identifier Source: org_study_id

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