Deze pagina is automatisch vertaald en de nauwkeurigheid van de vertaling kan niet worden gegarandeerd. Raadpleeg de Engelse versie voor een brontekst.

Een studie om de veiligheid, werkzaamheid, farmacokinetiek en farmacodynamiek van emicizumab te evalueren bij deelnemers met milde of matige hemofilie A zonder FVIII-remmers (HAVEN 6)

5 augustus 2026 bijgewerkt door: Hoffmann-La Roche

Een multicenter, open-label onderzoek om de veiligheid, werkzaamheid, farmacokinetiek en farmacodynamiek van emicizumab te evalueren bij patiënten met milde of matige hemofilie A zonder FVIII-remmers

Dit is een multicenter, open-label, eenarmig onderzoek dat is opgezet om de veiligheid, werkzaamheid, farmacokinetiek en farmacodynamiek van emicizumab te evalueren bij deelnemers met lichte of matige hemofilie A zonder remmers tegen factor VIII (FVIII).

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

73

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • België
      • Brussels, België, 1200
        • Cliniques Universitaires St-Luc
      • Leuven, België, 3000
        • UZ Leuven Gasthuisberg
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z1
        • Kaye Edmonton Clinic
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
        • Eastern Health - General Hospital
  • Duitsland
      • Bonn, Duitsland, 53127
        • Universitatsklinikum Bonn
      • München, Duitsland, 80336
        • Klinikum der Universität München, Campus Innenstadt
  • Frankrijk
      • Bron, Frankrijk, 69677
        • Hopital Cardio-vasculaire Louis Pradel
      • Le Kremlin-Bicêtre, Frankrijk, 94275
        • CH de Bicêtre
      • Paris, Frankrijk, 75015
        • Groupe Hospitalier Necker Enfants Malades
  • Nederland
      • Amsterdam, Nederland, 1105 AZ
        • Amsterdam UMC Location AMC
  • Polen
      • Warsaw, Polen, 02-776
        • Instytut Hematologii i Transfuzjologii
  • Spanje
      • Madrid, Spanje, 28046
        • Hospital Universitario La Paz
      • Seville, Spanje, 41013
        • Hospital Universitario Virgen del Rocío
  • Verenigd Koninkrijk
      • Cardiff, Verenigd Koninkrijk, CF14 4XW
        • Cardiff and Vale NHS Trust
      • London, Verenigd Koninkrijk, NW3 2QG
        • Royal Free Hospital
      • London, Verenigd Koninkrijk, WC1N 3HR
        • Great Ormond Street Hospital for Children NHS Foundation Trust
  • Verenigde Staten
    • California
      • Los Angeles, California, Verenigde Staten, 90027
        • Childrens Hospital LA
    • Georgia
      • Atlanta, Georgia, Verenigde Staten, 30308
        • Hemophilia of Georgia Center for Bleeding & Clotting Disorders
    • Indiana
      • Indianapolis, Indiana, Verenigde Staten, 46260
        • Indiana Hemophilia & Thrombosis center
    • Michigan
      • Ann Arbor, Michigan, Verenigde Staten, 48109
        • University of Michigan, C.S. Mott Children's Hospital
    • Washington
      • Seattle, Washington, Verenigde Staten, 98101
        • Washington Institute for Coagulation
  • Zuid-Afrika
      • Johannesburg, Zuid-Afrika, 2193
        • Charlotte Maxeke Johannesburg Hospital

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Kind
  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

Inclusiecriteria:

  • Diagnose van milde (FVIII-waarde tussen >5% en
  • Gewicht ≥3 kilogram (kg)
  • Behoefte aan profylaxe op basis van beoordeling door de onderzoeker
  • Een negatieve test voor remmer (d.w.z.
  • Geen gedocumenteerde remmer (d.w.z.
  • Documentatie van de details van profylactische of episodische FVIII-behandeling en van het aantal bloedingsepisoden gedurende ten minste de laatste 24 weken voorafgaand aan inschrijving
  • Adequate hematologische lever- en nierfunctie
  • Voor vrouwen in de vruchtbare leeftijd: afspraak om onthouding te blijven of anticonceptie te gebruiken (zoals gedefinieerd in het protocol) tijdens de behandelingsperiode en gedurende ten minste 24 weken na de laatste dosis van het onderzoeksgeneesmiddel

Uitsluitingscriteria:

  • Erfelijke of verworven bloedingsstoornis anders dan milde of matige congenitale hemofilie A
  • Geschiedenis van illegaal drugs- of alcoholmisbruik binnen 48 weken voorafgaand aan de screening, naar het oordeel van de onderzoeker
  • Vorige (in de laatste 12 maanden) of huidige behandeling voor trombo-embolische ziekte of tekenen van trombo-embolische ziekte
  • Andere aandoeningen die momenteel het risico op bloedingen of trombose kunnen verhogen
  • Geschiedenis van klinisch significante overgevoeligheid geassocieerd met monoklonale antilichaamtherapieën of componenten van de emicizumab-injectie
  • Geplande operatie tijdens de oplaaddosisfase van emicizumab (operaties bij deelnemers die emicizumab gebruiken vanaf week 5 zijn toegestaan)
  • Bekende hiv-infectie met CD4-tellingen
  • Gelijktijdige ziekte, aandoening, significante afwijking bij screeningevaluatie of laboratoriumtests, of behandeling die de uitvoering van het onderzoek zou kunnen verstoren, of die naar de mening van de onderzoeker een bijkomend onaanvaardbaar risico zou vormen bij het toedienen van het onderzoeksgeneesmiddel aan de deelnemer
  • Ontvangst van een van de volgende geneesmiddelen: Een onderzoeksgeneesmiddel om het risico op hemofiliebloedingen te behandelen of te verminderen binnen 5 halfwaardetijden na de laatste toediening van het geneesmiddel, met uitzondering van eerdere emicizumab-profylaxe; Een niet-hemofilie-gerelateerd onderzoeksgeneesmiddel binnen de afgelopen 30 dagen of 5 halfwaardetijden, welke korter is; of enig ander onderzoeksgeneesmiddel dat momenteel wordt toegediend of gepland is om te worden toegediend
  • Onvermogen om het onderzoeksprotocol na te leven naar de mening van de onderzoeker
  • Zwanger of borstvoeding gevend, of van plan zwanger te worden tijdens het onderzoek (vrouwen die zwanger kunnen worden moeten een negatief serumzwangerschapstestresultaat hebben binnen 7 dagen voorafgaand aan de start van het onderzoeksgeneesmiddel)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Emicizumab
Deelnemers met lichte en matige hemofilie A zonder factor VIII-remmers (FVIII-remmers) zullen worden ingeschreven voor het emicizumab-oplaaddosisregime, gevolgd door de voorkeur van de deelnemer voor een van de 3 onderhoudsdosisregimes.
Geneesmiddel: Emicizumab
Vier oplaaddoses emicizumab 3 milligram per kilogram lichaamsgewicht (mg/kg) zullen subcutaan (SC) eenmaal per week (QW) gedurende 4 weken worden toegediend, gevolgd door de voorkeur van de deelnemer voor een van de drie volgende SC-onderhoudsdosisregimes: 1,5 mg /kg QW, 3 mg/kg eenmaal per 2 weken (Q2W), of 6 mg/kg eenmaal per 4 weken (Q4W).
Andere namen:
  • Hemlibra
  • RO5534262
  • RG6013
  • ACE910

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Op modellen gebaseerd bloedingspercentage op jaarbasis voor behandelde bloedingen
Tijdsspanne: Vanaf de dag van de eerste dosis emicizumab tot ten minste 52 weken behandeling met emicizumab (mediane [spreiding, min-max] werkzaamheidsperiode: 55,64 [8,6-89,9] weken)
Het aantal behandelde bloedingen gedurende de werkzaamheidsperiode werd geschat als een bloedingspercentage op jaarbasis (ABR) met behulp van een negatief binomiaal regressiemodel, dat rekening houdt met verschillende follow-uptijden. Een behandelde bloeding werd gedefinieerd als een bloeding die direct werd gevolgd door een hemofiliemedicatie waarvan werd gemeld dat het een "behandeling voor bloeding" was. De 72-uursregel werd ingevoerd: twee bloedingen van hetzelfde type en op dezelfde anatomische locatie werden geteld als één bloeding als de tweede bloeding optrad binnen 72 uur na de laatste behandeling voor de eerste bloeding. Bloedingen als gevolg van een operatie/procedure werden uitgesloten.
Vanaf de dag van de eerste dosis emicizumab tot ten minste 52 weken behandeling met emicizumab (mediane [spreiding, min-max] werkzaamheidsperiode: 55,64 [8,6-89,9] weken)
Mean Calculated ABR for Treated Bleeds
Tijdsspanne: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated bleed was defined as a bleed that was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Median Calculated ABR for Treated Bleeds
Tijdsspanne: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated bleed was defined as a bleed that was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Gemiddelde berekende bloedingssnelheid op jaarbasis voor behandelde spontane bloedingen
Tijdsspanne: Vanaf de dag van de eerste dosis emicizumab tot ten minste 52 weken behandeling met emicizumab (mediane [spreiding, min-max] werkzaamheidsperiode: 55,64 [8,6-89,9] weken)
Het aantal behandelde spontane bloedingen gedurende de werkzaamheidsperiode wordt hier weergegeven als een berekend aantal bloedingen op jaarbasis (ABR) dat voor elke deelnemer op jaarbasis werd berekend met behulp van de volgende formule: ABR = (aantal bloedingen/aantal dagen tijdens de werkzaamheidsperiode) x 365,25 . Een behandelde spontane bloeding werd gedefinieerd als een behandelde bloeding (bloeding direct gevolgd door een hemofiliemedicatie die naar verluidt een "behandeling voor bloeding" is) zonder andere bekende bijdragende factor zoals trauma of procedure/operatie. De 72-uursregel werd ingevoerd: twee bloedingen van hetzelfde type en op dezelfde anatomische locatie werden geteld als één bloeding als de tweede bloeding optrad binnen 72 uur na de laatste behandeling voor de eerste bloeding. Bloedingen als gevolg van een operatie/procedure werden uitgesloten.
Vanaf de dag van de eerste dosis emicizumab tot ten minste 52 weken behandeling met emicizumab (mediane [spreiding, min-max] werkzaamheidsperiode: 55,64 [8,6-89,9] weken)
Mediaan berekend jaarlijks bloedingspercentage voor behandelde spontane bloedingen
Tijdsspanne: Vanaf de dag van de eerste dosis emicizumab tot ten minste 52 weken behandeling met emicizumab (mediane [spreiding, min-max] werkzaamheidsperiode: 55,64 [8,6-89,9] weken)
Het aantal behandelde spontane bloedingen gedurende de werkzaamheidsperiode wordt hier weergegeven als een berekend aantal bloedingen op jaarbasis (ABR) dat voor elke deelnemer op jaarbasis werd berekend met behulp van de volgende formule: ABR = (aantal bloedingen/aantal dagen tijdens de werkzaamheidsperiode) x 365,25 . Een behandelde spontane bloeding werd gedefinieerd als een behandelde bloeding (bloeding direct gevolgd door een hemofiliemedicatie die naar verluidt een "behandeling voor bloeding" is) zonder andere bekende bijdragende factor zoals trauma of procedure/operatie. De 72-uursregel werd ingevoerd: twee bloedingen van hetzelfde type en op dezelfde anatomische locatie werden geteld als één bloeding als de tweede bloeding optrad binnen 72 uur na de laatste behandeling voor de eerste bloeding. Bloedingen als gevolg van een operatie/procedure werden uitgesloten.
Vanaf de dag van de eerste dosis emicizumab tot ten minste 52 weken behandeling met emicizumab (mediane [spreiding, min-max] werkzaamheidsperiode: 55,64 [8,6-89,9] weken)
Percentage deelnemers dat de voorkeur geeft aan een SC-behandeling met Emicizumab, hun eerdere hemofilie IV-behandeling of geen voorkeur heeft, zoals beoordeeld door middel van het Emicizumab-voorkeurenonderzoek in week 17
Tijdsspanne: Week 17
De Emicizumab Preference Survey is een vragenlijst die geschikt is voor het beoogde doel, ontwikkeld door de sponsor om de voorkeur van de deelnemer vast te leggen voor behandeling met subcutane (SC) emicizumab, intraveneuze (IV) factor VIIII (FVIII) of geen voorkeur. De 95%-betrouwbaarheidsintervallen werden berekend met behulp van de Pearson-Clopper-methode.
Week 17
Percentage zorgverleners dat de voorkeur geeft aan een behandeling met SC Emicizumab, de eerdere hemofilie IV-behandeling van hun kind of geen voorkeur heeft, zoals beoordeeld aan de hand van het onderzoek naar de voorkeuren van Emicizumab in week 17
Tijdsspanne: Week 17
De Emicizumab Preference Survey is een vragenlijst die geschikt is voor het beoogde doel, ontwikkeld door de sponsor om de voorkeur van de verzorger vast te leggen voor de behandeling van hun kind met subcutane (SC) emicizumab, intraveneuze (IV) factor VIIII (FVIII) of geen voorkeur. De 95%-betrouwbaarheidsintervallen werden berekend met behulp van de Pearson-Clopper-methode.
Week 17
Verandering van baseline in gemiddelde dagelijkse piekactiviteitsduur in de loop van de tijd
Tijdsspanne: Baseline (week 1-2) en week 13 (week 12-13 periode), 25 (week 24-25 periode), 37 (week 36-37 periode) en 49 (week 48-49 periode)
Voor de beoordeling van fysieke activiteit kregen deelnemers ≥5 jaar de instructie om het accelerometrie-apparaat van de studie continu (24 uur/dag) elke dag om de pols te dragen gedurende de aangegeven perioden van 2 weken tijdens de studie. Een deelnemer werd geacht te voldoen aan de beoordelingen van fysieke activiteit als hij het onderzoeksapparaat continu (≥ 8 uur/dag) elke dag droeg gedurende ten minste 8 dagen van elk van de aangewezen perioden van 2 weken tijdens het onderzoek. Als dit nalevingscriterium op een bepaald tijdstip niet werd bereikt, werd de deelnemer niet opgenomen in de analyse van de aangewezen perioden van 2 weken waarin naleving niet werd bereikt. Dagelijkse metingen werden gemiddeld over het tijdspunt van 14 dagen. Het aantal activiteiten was een maat voor de versnelling die door het apparaat werd gemeten. De duur van de dagelijkse piekactiviteit werd gedefinieerd als de som van matige tot krachtige activiteit per dag (in minuten).
Baseline (week 1-2) en week 13 (week 12-13 periode), 25 (week 24-25 periode), 37 (week 36-37 periode) en 49 (week 48-49 periode)
Verandering ten opzichte van de uitgangswaarde in het gemiddelde dagelijkse aantal stappen in de loop van de tijd
Tijdsspanne: Basislijn (week 1-2) en week 13 (week 12-13), 25 (week 24-25), 37 (week 36-37) en 49 (week 48-49)
Voor de beoordeling van fysieke activiteit kregen deelnemers ≥5 jaar de instructie om het accelerometrie-apparaat van de studie continu (24 uur/dag) elke dag om de pols te dragen gedurende de aangegeven perioden van 2 weken tijdens de studie. Een deelnemer werd geacht te voldoen aan de beoordelingen van fysieke activiteit als hij het onderzoeksapparaat continu (≥ 8 uur/dag) elke dag droeg gedurende ten minste 8 dagen van elk van de aangewezen perioden van 2 weken tijdens het onderzoek. Als dit nalevingscriterium op een bepaald tijdstip niet werd bereikt, werd de deelnemer niet opgenomen in de analyse van de aangewezen perioden van 2 weken waarin naleving niet werd bereikt. Dagelijkse metingen werden gemiddeld over het tijdspunt van 14 dagen. Het aantal activiteiten was een maat voor de versnelling die door het apparaat werd gemeten.
Basislijn (week 1-2) en week 13 (week 12-13), 25 (week 24-25), 37 (week 36-37) en 49 (week 48-49)
Model-Based ABR for All Bleeds
Tijdsspanne: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
The number of all bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Mean Calculated ABR for All Bleeds
Tijdsspanne: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Median Calculated ABR for All Bleeds
Tijdsspanne: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Model-Based ABR for Treated Joint Bleeds
Tijdsspanne: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
The number of treated joint bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated joint bleed was defined as a bleed with type reported as "joint" based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Mean Calculated ABR for Treated Joint Bleeds
Tijdsspanne: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated joint bleed was defined as a bleed with type reported as "joint" based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Median Calculated ABR for Treated Joint Bleeds
Tijdsspanne: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated joint bleed was defined as a bleed with type reported as "joint" based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Model-Based ABR for Treated Target Joint Bleeds
Tijdsspanne: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
The number of treated target joint bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Mean Calculated ABR for Treated Target Joint Bleeds
Tijdsspanne: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Median Calculated ABR for Treated Target Joint Bleeds
Tijdsspanne: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Model-Based ABR for Treated Spontaneous Bleeds
Tijdsspanne: From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
The number of treated spontaneous bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated spontaneous bleed was defined as a treated bleed (bleed directly followed by a hemophilia medication reported to be a "treatment for bleed") with no other known contributing factor such as trauma or procedure/surgery. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
From the day of first emicizumab dose to at least 52 weeks of emicizumab treatment (median [range, min-max] efficacy period: 55.64 [8.6-89.9] weeks)
Long-term Efficacy of Emicizumab: Model-Based ABR for Treated Bleeds
Tijdsspanne: Median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of treated bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated bleed was defined as a bleed that was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
Median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy of Emicizumab: Mean Calculated ABR for Treated Bleeds
Tijdsspanne: Median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated bleed was defined as a bleed that was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
Median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy of Emicizumab: Median Calculated ABR for Treated Bleeds
Tijdsspanne: Median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of treated bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated bleed was defined as a bleed that was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
Median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy of Emicizumab: Model-Based ABR for All Bleeds
Tijdsspanne: median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of all bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy of Emicizumab: Mean Calculated ABR for All Bleeds
Tijdsspanne: median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy: Median Calculated ABR for All Bleeds
Tijdsspanne: median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of all bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. In this outcome measure, all bleeds are included, irrespective of treatment with coagulation factors, with the following exception: bleeds due to surgery/procedure are excluded. As "all bleeds" comprises both treated and non-treated bleeds, the 72-hour rule was implemented separately for treated and non-treated bleeds. For treated bleeds, the 72-hour rule meant that two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. For non-treated bleeds, the 72-hour rule was implemented by calculating a treatment-free period of 72 hours from the bleed itself.
median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy of Emicizumab: Model-Based ABR for Treated Joint Bleeds
Tijdsspanne: median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of treated joint bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated joint bleed was defined as a bleed with type reported as "joint" based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy of Emicizumab: Mean Calculated ABR for Treated Joint Bleeds
Tijdsspanne: median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated joint bleed was defined as a bleed with type reported as "joint" based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy of Emicizumab: Median Calculated ABR for Treated Joint Bleeds
Tijdsspanne: median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of treated joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated joint bleed was defined as a bleed with type reported as "joint" based on at least one of the following symptoms: increasing swelling or warmth of the skin over the joint and/or increasing pain, decreased range of motion, or difficulty using the joint compared with baseline, and the bleed was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy of Emicizumab: Model-Based ABR for Treated Target Joint Bleeds
Tijdsspanne: median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of treated target joint bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy of Emicizumab: Mean Calculated ABR for Treated Target Joint Bleeds
Tijdsspanne: median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy of Emicizumab: Median Calculated ABR for Treated Target Joint Bleeds
Tijdsspanne: median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of treated target joint bleeds over the efficacy period is presented here as a calculated ABR that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated target joint bleed was defined as a joint bleed in a target joint, which is a joint location where at least 3 bleeds have occurred over the last 24 weeks prior to study entry or an unresolved target joint (target joint that does not fulfil ≤2 bleeds into this joint within a consecutive 12-month period), and the bleed was directly followed by a hemophilia medication reported to be a "treatment for bleed". The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy of Emicizumab: Model-Based ABR for Treated Spontaneous Bleeds
Tijdsspanne: median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of treated spontaneous bleeds over the efficacy period was estimated as an ABR using a negative binomial regression model, which accounts for different follow-up times. A treated spontaneous bleed was defined as a treated bleed (bleed directly followed by a hemophilia medication reported to be a "treatment for bleed") with no other known contributing factor such as trauma or procedure/surgery. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy of Emicizumab: Mean Calculated ABR for Treated Spontaneous Bleeds
Tijdsspanne: median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated spontaneous bleed was defined as a treated bleed (bleed directly followed by a hemophilia medication reported to be a "treatment for bleed") with no other known contributing factor such as trauma or procedure/surgery. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
Long-term Efficacy of Emicizumab: Median Calculated ABR for Treated Spontaneous Bleeds
Tijdsspanne: median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
The number of treated spontaneous bleeds over the efficacy period is presented here as a calculated annualized bleed rate (ABR) that was annualized for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. A treated spontaneous bleed was defined as a treated bleed (bleed directly followed by a hemophilia medication reported to be a "treatment for bleed") with no other known contributing factor such as trauma or procedure/surgery. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location were counted as one bleed if the second bleed occurred within 72 hours from the last treatment for the first bleed. Bleeds due to surgery/procedure were excluded.
median [range, min-max] efficacy period: 156.07 [24.1-274] weeks
CATCH Questionnaire for Adult Participants: Change From Baseline in the Daily Activity Risk Perception (RP) and Impact Domain Scores Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and Study completion (SC)/Early discontinuation (ED) (up to approximately 274 weeks)
Comprehensive Assessment Tool of Challenges in Hemophilia (CATCH) was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥ 18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, the daily activity RP and impact domain has 48 items with each item scored on 4 or 5 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept and applying a linear transformation. The transformed scores range from 0-100 scale for both the RP and Impact. Higher scores indicating higher perceived risk of having a bleed while doing daily activities and higher impact of hemophilia on daily activities.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and Study completion (SC)/Early discontinuation (ED) (up to approximately 274 weeks)
CATCH Questionnaire for Adult Participants: Change From Baseline in the Social Activity RP and Impact Domain Scores Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥ 18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, the social activity RP and impact domain has 22 items with each item scored on 4 or 5 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept and applying a linear transformation. The transformed scores range from 0-100 scale for both the RP and Impact. Higher scores indicating higher perceived risk of having a bleed while doing social activities and higher impact of hemophilia on social activities.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Adult Participants: Change From Baseline in the Recreational Activity RP and Impact Domain Scores Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥ 18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, the recreational activity RP and impact domain has 32 items and a larger bank of additional items with each item scored on 4 or 5 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept and applying a linear transformation. The transformed scores range from 0-100 scale for both the RP and Impact. Higher scores indicating higher perceived risk of having a bleed while doing recreational activities and higher impact of hemophilia on recreational activities.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Adult Participants: Change From Baseline in the Work Impact (WI) and College Impact (CI) Domains Score Over Time
Tijdsspanne: WI: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks); CI: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥ 18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, work and college impact has 10 items and the items were scored on 4 or 5 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept & applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated impact of hemophilia on work and college activities.
WI: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks); CI: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Adult Participants: Change From Baseline in the Preoccupation Domain Score Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, preoccupation has 10 items which were scored on 4 or 5 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept & applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated greater preoccupation related to hemophilia.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Adult Participants: Change From Baseline in the Treatment Burden Domain Score Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, treatment burden has 8 items which were scored on 4 or 5 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept & applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated greater perceived burden of the hemophilia treatment.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain Associated With a Bleed Over Time
Tijdsspanne: Baseline, Weeks 25, 49, 61, 85, 121, 133, 157 and 169 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, the pain domain consisting of five items, assessed using an 11-point numeric rating scale where 0 = no pain and 10 = pain as bad as you can imagine. The data reported here are from participants who answered the following question: "Did you get a bleed in the past 7 days?" If the response was yes, participants were asked to rate their pain by selecting the number that best described the pain associated with the bleed. Data is reported only for categories/timepoints with non-zero values.
Baseline, Weeks 25, 49, 61, 85, 121, 133, 157 and 169 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain in Target Joints Over Time
Tijdsspanne: Baseline, Weeks 1, 13, 25, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, the pain domain consists of five items, assessed using an 11-point numeric rating scale where 0 = no pain and 10 = pain as bad as you can imagine. The data reported here are from participants who answered the following question "Do you have target joints?" (If yes, please rate your pain by picking the number that best describes your pain in your target joint(s) over the past 7 days). Data is reported only for categories/timepoints with non-zero values.
Baseline, Weeks 1, 13, 25, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain at Its Worst Over Time
Tijdsspanne: Baseline, Weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, pain domain consists of five items, assessed using an 11-point numeric rating scale where 0 = no pain and 10 = pain as bad as you can imagine. The data reported here are from participants who answered the following question "Please rate your pain by picking the number that best describes your pain at its WORST over the past 7 days". Data is reported only for categories/timepoints with non-zero values.
Baseline, Weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain at Its Least Over Time
Tijdsspanne: Baseline, Weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, pain domain consists of five items, assessed using an 11-point numeric rating scale where 0 = no pain and 10 = pain as bad as you can imagine. The data reported here are from participants who answered the following question "Please rate your pain by picking the number that best describes your pain at its LEAST over the past 7 days." Data is reported only for categories/timepoints with non-zero values.
Baseline, Weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Adult Participants: Number of Participants by Responses to Their Level of Pain at Its Least on the Average Over Time
Tijdsspanne: Baseline, Weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on adult participants (aged ≥18 years). The adult version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, work impact, preoccupation, treatment burden, and pain. Of this, the pain domain consists of five items, assessed using an 11-point numeric rating scale where 0 = no pain and 10 = pain as bad as you can imagine. The data reported here are from participants who answered the following question "Please rate your pain by picking the number that best describes your pain at its average over the past 7 days". Data is reported only for categories/timepoints with non-zero values.
Baseline, Weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Daily Activity RP and Impact Domain Score Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain). Of this, daily activity RP and impact has 38 items with each item scored on 3 or 4 points ordinal scale. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept and applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicating higher perceived risk of having a bleed while doing daily activities and higher impact of hemophilia on daily activities.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Social Activity Risk Perception and Impact Domain Score Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain). Of this, social activity RP and impact has 16 items which were scored on 3 or 4 points ordinal scale. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept & applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated higher perceived risk of having a bleed while doing social activities and higher impact of hemophilia on social activities.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Recreational Activity RP and Impact Domain Score Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain. Of this, recreational activity RP & impact has 34 items + larger bank of additional items. The items were scored on 3 or 4 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept & applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated higher perceived risk of having a bleed while doing recreational activities and higher impact of hemophilia on recreational activities.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the School Impact Domain Score Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain. Of this, school impact has 11 items and the items were scored on 3 or 4 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept & applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated higher impact of hemophilia on school activities.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Preoccupation Domain Score Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain. Of this, preoccupation has 3 items which were scored on 3 or 4 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept & applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated greater preoccupation related to hemophilia.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Pediatric Participants: Change From Baseline in the Treatment Burden Domain Score Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain. Of this, treatment burden has 7 items which were scored on 3 or 4 points ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept & applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated lower perceived burden of the hemophilia treatment.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Pediatric Participants: Number of Participants by Responses to Their Level of Hurt Associated With a Bleed Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 85, 97, 109, 121, 133, 145 and 157
CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain). Of this, pain domain (Hurt) consists of two items, assessed using an 11-point numeric rating scale where 0 = no hurt and 10 = a lot of hurt. The data reported here are from participants who answered the following question "Did you get a bleed in the past 7 days? ( If yes, how much did the bleed hurt?)." Data is reported only for categories/timepoints with non-zero values.
Baseline, Weeks 13, 25, 37, 49, 61, 85, 97, 109, 121, 133, 145 and 157
CATCH Questionnaire for Pediatric Participants: Number of Participants by Responses to Their Level of Hurt at Its Worst Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145,157, 169 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on pediatric participants (aged 8-17 years). The pediatric version has 7 domains (daily activity RP and impact, social activity RP and impact, recreational activity RP and impact, school impact, preoccupation, treatment burden, and pain. Of this, pain domain (Hurt) consists of two items, assessed using an 11-point numeric rating scale where 0 = no hurt and 10 = a lot of hurt. The data reported here are from participants who answered the following question "What is the WORST that your body has hurt over the past 7 days". Data is reported only for categories/timepoints with non-zero values.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145,157, 169 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Caregivers: Change From Baseline in the Preoccupation Domain Score Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on caregivers of pediatric participants (aged <8 years). The caregiver version has 2 domains (preoccupation and treatment burden). Of this, preoccupation has 13 items with each of the items were scored on 4 or 5 ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept and applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated greater preoccupation related to hemophilia.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH Questionnaire for Caregivers: Change From Baseline in the Treatment Burden Domain Score Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
CATCH was used to measure the effect of hemophilia and its treatment on caregivers of pediatric participants (aged <8 years). The caregiver version has 2 domains (preoccupation and treatment burden). Of this, treatment burden has 8 items which were scored on 4 or 5 ordinal scales. Raw domain scores were obtained by calculating the mean of the item scores for all items within the corresponding concept and applying a linear transformation. The transformed scores range from 0-100 scale. Higher scores indicated greater perceived burden of the hemophilia treatment.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
Change From Baseline in Hemophilia Joint Health Scores Over Time
Tijdsspanne: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
The HJHS measures joint health of the joints (knees, ankles, and elbows) most commonly affected by bleeding in hemophilia. The HJHS 2.1 provides joint specific total scores which are added to obtain the sum of joints totals and also a global gait score. These two scores are then added to obtain HJHS total score. The minimum score per joint is 0, the maximum score is 20. In addition, Gait is scored on a scale from 0 to 4 based on the number of skills that are not within the normal limits. The total score is the sum of scores across all six joints plus the gait score (range from 0 to 124, with 0 being normal and 124 being the most severe disease). A higher score indicates worse joint health.
Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, 109,121, 133, 145, 157, 169 and SC/ED (up to approximately 274 weeks)
Menstrual Bleed Questionnaire (MBQ) for Female Participants of Childbearing Potential: Change From Baseline in the MBQ Total Score Over Time
Tijdsspanne: Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 104, 109, 113, 117, 121, 125, 129, 133, 137, 141 and145
The MBQ is a validated measure for menorrhagia and used to assess impact on the menstrual bleed-related heaviness, pain, irregularity, and quality of life (QoL). The MBQ is a 20-item measure covering four aspects regarding heavy menstrual bleeding: heaviness (8 items), QoL (8 items), irregularity (3 item), and pain (1 item). The MBQ score ranges from 0 to 75. Higher scores indicate a worse quality of life and more severe symptoms.
Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 104, 109, 113, 117, 121, 125, 129, 133, 137, 141 and145
MBQ for Female Participants of Childbearing Potential: Change From Baseline in the Heaviness Subscale Score Over Time
Tijdsspanne: Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 89, 93, 97, 101, 104, 109, 113, 121, 125, 129, 133 and 137 (up to approximately 274 weeks)
The MBQ is a validated measure for menorrhagia and used to assess impact on the menstrual bleed-related heaviness, pain, irregularity, and quality of life (QoL). The MBQ is a 20-item measure covering four aspects regarding heavy menstrual bleeding: heaviness (8 items), QoL (8 items), irregularity (3 item), and pain (1 item). The total score for heaviness subscale ranges from 0 to 29. Higher score indicates more heavy bleeding.
Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 89, 93, 97, 101, 104, 109, 113, 121, 125, 129, 133 and 137 (up to approximately 274 weeks)
MBQ for Female Participants of Childbearing Potential: Change From Baseline in the QoL Subscale Score Over Time
Tijdsspanne: Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 104, 109, 113, 117, 121, 125, 129, 133, 137, 141 and 145
The MBQ is a validated measure for menorrhagia and used to assess impact on the menstrual bleed-related heaviness, pain, irregularity, and quality of life (QoL). The MBQ is a 20-item measure covering four aspects regarding heavy menstrual bleeding: heaviness (8 items), QoL (8 items), irregularity (3 item), and pain (1 item). The total score for QoL subscale ranges from 0 to 37. Higher scores indicate a worse QoL.
Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 104, 109, 113, 117, 121, 125, 129, 133, 137, 141 and 145
MBQ for Female Participants of Childbearing Potential: Change From Baseline in the Irregularity Subscale Score Over Time
Tijdsspanne: Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 104, 109, 113, 117, 121, 125, 129, 133, 137, 141 and 145
The MBQ is a validated measure for menorrhagia and used to assess impact on the menstrual bleed-related heaviness, pain, irregularity, and quality of life (QoL). The MBQ is a 20-item measure covering four aspects regarding heavy menstrual bleeding: heaviness (8 items), QoL (8 items), irregularity (3 item), and pain (1 item). The total score for irregularity subscale ranges from 0 to 6. Higher score indicates more irregularity.
Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 104, 109, 113, 117, 121, 125, 129, 133, 137, 141 and 145
MBQ for Female Participants of Childbearing Potential: Change From Baseline in the Pain Subscale Score Over Time
Tijdsspanne: Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 89, 93, 97, 101, 104, 109, 113, 121, 125, 129, 133 and 137
The MBQ is a validated measure for menorrhagia and used to assess impact on the menstrual bleed-related heaviness, pain, irregularity, and quality of life (QoL). The MBQ is a 20-item measure covering four aspects regarding heavy menstrual bleeding: heaviness (8 items), QoL (8 items), irregularity (3 item), and pain (1 item). The total score for pain subscale ranges from 0 to 3. Higher score indicates severe pain.
Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 89, 93, 97, 101, 104, 109, 113, 121, 125, 129, 133 and 137
Menstruation Diary With the Pictorial Blood Assessment Chart (PBAC) for Female Participants of Childbearing Potential: PBAC Scores Over Time
Tijdsspanne: Baseline and monthly (on days of menstruation) until Study Completion (up to approximately 247 weeks)
The Menstruation Diary used a PBAC, which has shown good correlation with menstrual blood loss. The PBAC is a chart that records the occurrence and size of clots, and the number of episodes of heavy bleeding (flooding), as well as depicts the amount of blood loss during a cycle.The PBAC records pad and tampon use (as either light [1 point], medium [5 points], or heavy [10 points] flow), clots (small [1 point] or large [5 points]), and flooding episodes (1 point each) which can be recorded as many times as necessary any day of the month. The PBAC is scored from 0 (no bleeding) onwards, with a score of >100 defining abnormal coagulation and heavy menstrual bleeding (corresponds to >80ml of blood loss per menstrual cycle).
Baseline and monthly (on days of menstruation) until Study Completion (up to approximately 247 weeks)
Number of Participants With at Least One Adverse Event by Severity, According to the World Health Organization (WHO) Toxicity Grading Scale
Tijdsspanne: From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. As per WHO toxicity grading, Grade 1= mild, 2= moderate, 3=severe, 4=life threatening.
From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks)
Number of Participants With Adverse Events Leading to Study Drug Discontinuation
Tijdsspanne: From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.
From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks)
Number of Participants With at Least One Thromboembolic Event
Tijdsspanne: From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. The following signs and symptoms were recognized as potential thromboembolism (i.e., dyspnea, chest pain, leg pain, or swelling; or if in the head, headache, numbness in the face, eye pain or swelling, or vision impairment).
From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks)
Number of Participants With at Least One Event of Thrombotic Microangiopathy
Tijdsspanne: From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. TMA is used to describe a group of disorders with clinical features of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage that can include the kidneys, gastrointestinal system, central nervous system, etc.
From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks)
Number of Participants With at Least One Injection-Site Reaction by Severity, According to the WHO Toxicity Grading Scale
Tijdsspanne: From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Injection-site reactions are defined as AEs related that occur within 24 hours after study drug administration and are judged to be related to the study drug injection. Local injection-site reactions included erythema, hematoma, rash, discomfort, pain, and pruritus and were mostly of mild and moderate intensity. As per WHO toxicity grading, Grade 1= mild, 2= moderate, 3=severe, 4=life threatening.
From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks)
Number of Participants With at Least One Severe Hypersensitivity, Anaphylaxis, and Anaphylactoid Event
Tijdsspanne: From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.
From enrollment until final completion date cutoff (median [range, min-max] observation period: 156.21 [24.1 - 274.0] weeks)
Number of Participants With at Least One Shifts in Clinical Laboratory Parameters From Baseline WHO Toxicity Scale Grade 0-2 to Post-baseline Grade 3 or 4
Tijdsspanne: Up to approximately 274 weeks
An abnormal laboratory value was defined as a laboratory test result outside of the normal range for hematology or serum chemistry parameters. The WHO toxicity grading scale, which ranges from Grades 1 to 4 (least severe to most severe, respectively; Grade 0 is within normal range), was used for assessing the severity of laboratory abnormalities and adverse events (WHO 2003). Not every laboratory abnormality qualified as an adverse event; an abnormality was reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment.
Up to approximately 274 weeks
Number of Participants With at Least One Adverse Events of Changes From Baseline in Vital Signs
Tijdsspanne: Up to approximately 274 weeks
The number of participants with adverse events of changes from baseline in vital signs is reported here. Vital signs measurements consisted of heart and respiratory rate, temperature, and systolic and diastolic blood pressures, with an abnormal vital sign value being outside of the normal range. An abnormal vital sign result was reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption or discontinuation); resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. All of the adverse events reported here were assessed independently by the investigator as not related to treatment with emicizumab.
Up to approximately 274 weeks
Change From Baseline in Electrocardiogram (ECG) Parameters Over Time: QT, QTcB, QTcF, RR, PR, and QRS Intervals
Tijdsspanne: Baseline, Weeks 5, 25, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181, SC/ED (up to approximately 274 weeks)
Baseline, Weeks 5, 25, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181, SC/ED (up to approximately 274 weeks)
Change From Baseline in Heart Rate Over Time, as Measured by ECG
Tijdsspanne: Baseline, Weeks 5, 25, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181, SC/ED (up to approximately 274 weeks)
Baseline, Weeks 5, 25, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181, SC/ED (up to approximately 274 weeks)
Plasma Trough Concentration (Ctrough) of Emicizumab Over Time
Tijdsspanne: Pre-dose at Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169 and 181 (up to approximately 274 weeks)
Pre-dose at Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169 and 181 (up to approximately 274 weeks)
Number of Participants With Anti-Drug Antibodies Against Emicizumab at Baseline and Post-Baseline
Tijdsspanne: Baseline, Weeks 5, 13, 25, 33, 41, 49, 61, 73, 85, 97, 109, 121, 133, 145, 169, 181 and SC/ED (up to approximately 274 weeks)
Participants were considered to be ADA positive if they were ADA negative at baseline but develop an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater than the titer of the baseline sample (treatment-enhanced ADA response). The sum of all visits has been reported here.
Baseline, Weeks 5, 13, 25, 33, 41, 49, 61, 73, 85, 97, 109, 121, 133, 145, 169, 181 and SC/ED (up to approximately 274 weeks)
Number of Participants Who Develop Anti-FVIII Inhibitors Over Time
Tijdsspanne: Up to approximately 274 weeks
Central laboratory measurement of anti-FVIII inhibitory antibodies (inhibitors) was performed using a Chromogenic Bethesda Assay (CBA). Participants who develop anti-FVIII inhibitors (titer ≥ 0.6 Bethesda units per milliliter [BU/mL]) following study drug administration were summarized.
Up to approximately 274 weeks

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Hoffmann-La Roche

Onderzoekers

  • Studie directeur: Clinical Trials, Hoffmann-La Roche

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

10 februari 2020

Primaire voltooiing (Werkelijk)

30 oktober 2021

Studie voltooiing (Werkelijk)

19 december 2025

Studieregistratiedata

Eerst ingediend

7 november 2019

Eerst ingediend dat voldeed aan de QC-criteria

7 november 2019

Eerst geplaatst (Werkelijk)

12 november 2019

Updates van studierecords

Laatste update geplaatst (Werkelijk)

27 augustus 2026

Laatste update ingediend die voldeed aan QC-criteria

5 augustus 2026

Laatst geverifieerd

1 augustus 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • BO41423
  • 2019 (Subsidie/contract van de Amerikaanse NIH: Chief Medical Office (CMO) Alberta Health Services)
  • 2023 (Subsidie/contract van de Amerikaanse NIH: GRAMMY Museum Foundation)
  • 2019-002179-32 (EudraCT-nummer)
  • 2023-506610-52-00 (Register-ID: EU CT Number)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

JA

Beschrijving IPD-plan

Gekwalificeerde onderzoekers kunnen via het aanvraagplatform (www.vivli.org) toegang vragen tot gegevens op individueel patiëntniveau. Meer details over de criteria van Roche voor in aanmerking komende studies zijn hier beschikbaar (https://vivli.org/ourmember/roche/).

Zie hier (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm) voor meer informatie over het wereldwijde beleid van Roche inzake het delen van klinische onderzoeksinformatie en hoe u toegang kunt vragen tot verwante klinische onderzoeksdocumenten.

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Abonneren