Ignite Creation Date:
2025-12-24 @ 5:03 PM
Ignite Modification Date:
2025-12-27 @ 6:50 AM
Study NCT ID:
NCT04590950
Status:
COMPLETED
Last Update Posted:
2025-09-12
First Post:
2020-07-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Dosage and PD Study of Eftrenonacog-alfa
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D002836', 'term': 'Hemophilia B'}], 'ancestors': [{'id': 'D025861', 'term': 'Blood Coagulation Disorders, Inherited'}, {'id': 'D001778', 'term': 'Blood Coagulation Disorders'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D020147', 'term': 'Coagulation Protein Disorders'}, {'id': 'D006474', 'term': 'Hemorrhagic Disorders'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D040181', 'term': 'Genetic Diseases, X-Linked'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITHOUT_DNA', 'description': 'Citrated plasma samples'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'RETROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 15}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-12-18', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2020-03-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-09-05', 'studyFirstSubmitDate': '2020-07-08', 'studyFirstSubmitQcDate': '2020-10-15', 'lastUpdatePostDateStruct': {'date': '2025-09-12', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2020-10-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-03-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'FIX activity levels', 'timeFrame': 'One month', 'description': '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)'}], 'secondaryOutcomes': [{'measure': 'Thrombin generation assay', 'timeFrame': 'One month', 'description': '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.\n\nThrombin 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)'}, {'measure': 'Thrombin generation assay', 'timeFrame': 'One month', 'description': 'microplate fluorometer, time to peak'}, {'measure': 'Thrombin generation assay', 'timeFrame': 'One month', 'description': 'microplate fluorometer, peak height'}, {'measure': 'Thrombin generation assay', 'timeFrame': 'One month', 'description': 'microplate fluorometer, endogenous thrombin potential'}, {'measure': 'Thrombin generation assay', 'timeFrame': 'One month', 'description': 'microplate fluorometer, velocity'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Chromogenic assay', 'Extended half-life product', 'Fc fusion protein', 'One-stage clotting assay', 'Pharmacodynamics'], 'conditions': ['Severe Haemophilia B']}, 'referencesModule': {'references': [{'pmid': '31418967', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '25144892', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '28264199', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '15735797', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '30536630', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '20731726', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '22776238', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '33249076', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nWith 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.\n\nUnlike 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.\n\nHence 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Severe haemophilia B patients', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* severe haemophilia B patients\n* treated with eftrenonacog-alfa\n\nExclusion Criteria:\n\n* any other haemostatic or replacement therapy'}, 'identificationModule': {'nctId': 'NCT04590950', 'acronym': 'BIOPAL', 'briefTitle': 'Dosage and PD Study of Eftrenonacog-alfa', 'organization': {'class': 'OTHER', 'fullName': 'Assistance Publique - Hôpitaux de Paris'}, 'officialTitle': 'Monitoring and Pharmacodynamics Effect of Recombinant Factor IX Fc in Severe Haemophilia B Patients: a Real-life Study', 'orgStudyIdInfo': {'id': 'APHP191124'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Single-group study', 'description': 'Severe haemophilia B patients substituted with eftrenonacog-alfa', 'interventionNames': ['Other: Non interventional study']}], 'interventions': [{'name': 'Non interventional study', 'type': 'OTHER', 'description': 'Non interventional study', 'armGroupLabels': ['Single-group study']}]}, 'contactsLocationsModule': {'locations': [{'zip': '75014', 'city': 'Paris', 'country': 'France', 'facility': "Service d'hématologie biologique - Hôpital Cochin", 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assistance Publique - Hôpitaux de Paris', 'class': 'OTHER'}, 'collaborators': [{'name': 'URC-CIC Paris Descartes Necker Cochin', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}