protocolSection identificationModule nctId: NCT06320626, orgStudyIdInfo id: 22-571, briefTitle: Pharmacokinetic-guided Dosing of Emicizumab, acronym: DosEmi, statusModule overallStatus: RECRUITING, startDateStruct date: 2022-09-08, primaryCompletionDateStruct date: 2026-03, completionDateStruct date: 2026-08, studyFirstPostDateStruct date: 2024-03-20, lastUpdatePostDateStruct date: 2024-03-20, sponsorCollaboratorsModule leadSponsor name: Kathelijn Fischer, class: OTHER, collaborators name: Erasmus Medical Center, collaborators name: Amsterdam University Medical Center, collaborators name: Leiden University Medical Center, collaborators name: Radboud University Medical Center, collaborators name: Maastricht University Medical Center, collaborators name: University Medical Center Groningen, collaborators name: HagaZiekenhuis, collaborators name: Dutch Society of Haemophilia Patients, descriptionModule briefSummary: The goal of this multicentre, prospective, open-label, cross-over clinical study is to determine whether individualized PK-guided dosing of emicizumab is non-inferior to conventional dosing of emicizumab in the prevention of bleeding in congenital haemophilia A patients., conditionsModule conditions: Hemophilia A With Inhibitor, conditions: Hemophilia A Without Inhibitor, conditions: Hemophilia A, Severe, conditions: Adolescent, conditions: Child, conditions: Adult, designModule studyType: INTERVENTIONAL, phases: PHASE4, designInfo allocation: NON_RANDOMIZED, interventionModel: CROSSOVER, interventionModelDescription: * PK-guided dosing - Intervention group (12M): Subjects with emicizumab concentration of ≥ 40 μg/mL will receive individualized PK-guided dose reduction of emicizumab targeted at a Ctrough of 30μg/mL. The validated population PK model is based on published population PK and PK/PD modelling studies. (9,10,15)* PK-Guided dosing - Non-intervention group (12M): Subjects with emicizumab concentration of 25-39 μg/mL will continue on their current dose regimen and will be followed according to the same assessment schedule as the Intervention Group. Only subjects with emicizumab plasma concentration \< 25 μg/mL will be adjusted in dosing regimen according to local protocol. These subjects will be followed for selective safety data only., primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 95, type: ESTIMATED, armsInterventionsModule interventions name: Emicizumab - PK-guided dose reduction, interventions name: Emicizumab - Dosis continuation group, interventions name: Emicizumab - Dose adjustment group, outcomesModule primaryOutcomes measure: Proportion of patients without treated bleeds, secondaryOutcomes measure: Proportion of patients without treated bleeds, secondaryOutcomes measure: Proportion of patients without spontaneous joint- or muscle bleeds, secondaryOutcomes measure: Annualized bleeding rate (ABR) of treated bleeds, including joint bleeds and sport-induced bleeds, secondaryOutcomes measure: To compare cost-effectiveness between conventional dosing and individualized PK-guided dosing of emicizumab, secondaryOutcomes measure: To assess the cumulative number of coagulation factor (sc. and/or iv.) of per year., secondaryOutcomes measure: To assess the performance of the population PK model, secondaryOutcomes measure: To investigate whether direct joint health remains stable measured by physical examination when switching to lower-dosed emicizumab compared to conventional treatment, secondaryOutcomes measure: To investigate whether direct joint health remains stable measured by ultrasound when switching to lower-dosed emicizumab compared to conventional treatment, secondaryOutcomes measure: To investigate if indirect joint health, as measured by biomarkers, remains stable when switching to lower doses of emicizumab compared to conventional treatment., secondaryOutcomes measure: To investigate if indirect joint health, as measured by biomarkers, remains stable when switching to lower doses of emicizumab compared to conventional treatment., secondaryOutcomes measure: To investigate whether Health Related Quality of Life (HR-QoL) are similar in patients receiving conventional dosing compared with PK-guided dosing of emicizumab., secondaryOutcomes measure: To investigate whether Health Related Quality of Life (HR-QoL) are similar in patients receiving conventional dosing compared with PK-guided dosing of emicizumab., secondaryOutcomes measure: To investigate whether sports participation are similar in patients receiving conventional dosing compared with PK-guided dosing of emicizumab., secondaryOutcomes measure: To investigate whether thrombin generation parameters can be used as a pharmacodynamic (PD) biomarker for emicizumab treatment efficacy., secondaryOutcomes measure: To assess and monitor pain during emicizumab administration, eligibilityModule sex: MALE, minimumAge: 1 Year, stdAges: CHILD, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Radboud University Medical Center, status: RECRUITING, city: Nijmegen, state: Gelderland, zip: 6525 GA, country: Netherlands, contacts name: Saskia Schols, Dr, MD, role: CONTACT, phone: +310 24 361 8823, email: Saskia.Schols@radboudumc.nl, contacts name: Saskia Schols, Dr, MD, role: SUB_INVESTIGATOR, geoPoint lat: 51.8425, lon: 5.85278, locations facility: Maastricht University Medical Center, status: RECRUITING, city: Maastricht, state: Limburg, country: Netherlands, contacts name: Floor Moenen, Dr, MD, role: CONTACT, phone: +31433876543, email: floor.moenen@mumc.nl, contacts name: Floor Moenen, Dr, MD, role: SUB_INVESTIGATOR, geoPoint lat: 50.84833, lon: 5.68889, locations facility: Amsterdam University Medical Center, status: RECRUITING, city: Amsterdam, state: Noord-Holland, zip: 1105 AZ, country: Netherlands, contacts name: Michiel Coppens, Dr, MD, role: CONTACT, phone: +31(0)20 566 5964, email: m.coppens@amsterdamumc.nl, contacts name: Michiel Coppens, Dr, MD, role: SUB_INVESTIGATOR, geoPoint lat: 52.37403, lon: 4.88969, locations facility: HagaZiekenhuis, status: RECRUITING, city: Den Haag, state: Zuid-Holland, zip: 2545 CH, country: Netherlands, contacts name: Paula Ypma, MD, role: CONTACT, phone: +310702102620, email: haematologie@hagaziekenhuis.nl, contacts name: Paula Ypma, MD, role: SUB_INVESTIGATOR, geoPoint lat: 52.07667, lon: 4.29861, locations facility: Leids Universitair Medisch Centrum, status: RECRUITING, city: Leiden, state: Zuid-Holland, zip: 2300 RC, country: Netherlands, contacts name: Paul den Exter, Dr, MD, role: CONTACT, phone: +31 (0)71 526 1850, email: p.l.den_exter@lumc.nl, contacts name: Paul den Exter, Dr, MD, role: SUB_INVESTIGATOR, geoPoint lat: 52.15833, lon: 4.49306, locations facility: Erasmus University Medical Center, status: RECRUITING, city: Rotterdam, state: Zuid-Holland, zip: 3000CA, country: Netherlands, contacts name: Marjon Cnossen, Dr., MD, role: CONTACT, phone: +31107040113, email: m.cnossen@erasmusmc.nl, contacts name: Marjon Cnossen, Dr. MD, role: SUB_INVESTIGATOR, geoPoint lat: 51.9225, lon: 4.47917, locations facility: University Medical Center Groningen, status: RECRUITING, city: Groningen, zip: 9700 RB, country: Netherlands, contacts name: Louise Hooimeijer, MD, role: CONTACT, phone: +310-503612740, email: h.l.hooimeijer@umcg.nl, contacts name: Louise Hooimeijer, MD, role: SUB_INVESTIGATOR, geoPoint lat: 53.21917, lon: 6.56667, locations facility: University Medical Center Utrecht, status: RECRUITING, city: Utrecht, country: Netherlands, contacts name: Kathelijn Fischer, Dr, MD, role: CONTACT, phone: +31887558450, email: K.Fischer@umcutrecht.nl, contacts name: Konrad van der Zwet, MD, role: CONTACT, phone: +31650124691, email: dosemi@umcutrecht.nl, contacts name: Kathelijn Fischer, Dr, MD, role: PRINCIPAL_INVESTIGATOR, contacts name: Konrad van der Zwet, MD, role: SUB_INVESTIGATOR, contacts name: Lize F.D. van Vulpen, Dr, MD, role: SUB_INVESTIGATOR, contacts name: Roger E.G. Schutgens, Prof, MD, role: SUB_INVESTIGATOR, contacts name: Paul van der Valk, MD, role: SUB_INVESTIGATOR, contacts name: Karin P.M. van Galen, Dr, MD, role: SUB_INVESTIGATOR, contacts name: Nanda Uitslager, Msc, role: SUB_INVESTIGATOR, geoPoint lat: 52.09083, lon: 5.12222, hasResults: False