Dosage and PD Study of Eftrenonacog-alfa (BIOPAL)

October 15, 2020 updated by: Assistance Publique - Hôpitaux de Paris

Monitoring and Pharmacodynamics Effect of Recombinant Factor IX Fc in Severe Haemophilia B Patients: a Real-life Study

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Anticipated)

15

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Paris, France, 75014
        • Service d'hématologie biologique - Hôpital Cochin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Severe haemophilia B patients

Description

Inclusion Criteria:

  • severe haemophilia B patients
  • treated with eftrenonacog-alfa

Exclusion Criteria:

  • any other haemostatic or replacement therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Single-group study
Severe haemophilia B patients substituted with eftrenonacog-alfa
Other: Non interventional study
Non interventional study

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
FIX activity levels
Time Frame: 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)
One month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Thrombin generation assay
Time Frame: One month

Thrombin generation assay is performed using a microplate fluorometer. Plasma samples are run using 20 μL low phospholipids reagent (PPP-reagent) (1 μM tissue factor and 4 micromoles (μM )phospholipid vesicles) or 20 μL Thrombin Calibrator. Assay is initiated by auto dispensing 20 μL of Fluo-Substrate solution containing calcium ions and fluorogenic substrate, Z-Gly-Gly-Arg-7-amino-4-methylcoumarin. Generated thrombin cleaves the substrate and fluorescence increase is monitored at 37 °C for 60 min with a measurement every 20 seconds.

Thrombin scope®, version 5.0.0.742 is used to calculate the amount of thrombin generated over time taking into account for each sample the calibrator activity. Consequently, five parameters are reported by the Thrombin scope® the fist is lag time (LT; in min)
One month
Thrombin generation assay
Time Frame: One month
microplate fluorometer, time to peak
One month
Thrombin generation assay
Time Frame: One month
microplate fluorometer, peak height
One month
Thrombin generation assay
Time Frame: One month
microplate fluorometer, endogenous thrombin potential
One month
Thrombin generation assay
Time Frame: One month
microplate fluorometer, velocity
One month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 1, 2020

Primary Completion (Anticipated)

December 1, 2020

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

July 8, 2020

First Submitted That Met QC Criteria

October 15, 2020

First Posted (Actual)

October 19, 2020

Study Record Updates

Last Update Posted (Actual)

October 19, 2020

Last Update Submitted That Met QC Criteria

October 15, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP191124

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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