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Uno studio per valutare la sicurezza, l'efficacia, la farmacocinetica e la farmacodinamica di Emicizumab nei partecipanti con emofilia A lieve o moderata senza inibitori del FVIII (HAVEN 6)

5 agosto 2026 aggiornato da: Hoffmann-La Roche

Uno studio multicentrico in aperto per valutare la sicurezza, l'efficacia, la farmacocinetica e la farmacodinamica di Emicizumab in pazienti con emofilia A lieve o moderata senza inibitori del FVIII

Questo è uno studio multicentrico, in aperto, a braccio singolo progettato per valutare la sicurezza, l'efficacia, la farmacocinetica e la farmacodinamica di emicizumab nei partecipanti con emofilia A lieve o moderata senza inibitori contro il fattore VIII (FVIII).

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

73

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Belgio
      • Brussels, Belgio, 1200
        • Cliniques Universitaires St-Luc
      • Leuven, Belgio, 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
  • Francia
      • Bron, Francia, 69677
        • Hopital Cardio-vasculaire Louis Pradel
      • Le Kremlin-Bicêtre, Francia, 94275
        • CH de Bicêtre
      • Paris, Francia, 75015
        • Groupe Hospitalier Necker Enfants Malades
  • Germania
      • Bonn, Germania, 53127
        • Universitatsklinikum Bonn
      • München, Germania, 80336
        • Klinikum der Universität München, Campus Innenstadt
  • Olanda
      • Amsterdam, Olanda, 1105 AZ
        • Amsterdam UMC Location AMC
  • Polonia
      • Warsaw, Polonia, 02-776
        • Instytut Hematologii i Transfuzjologii
  • Regno Unito
      • Cardiff, Regno Unito, CF14 4XW
        • Cardiff and Vale NHS Trust
      • London, Regno Unito, NW3 2QG
        • Royal Free Hospital
      • London, Regno Unito, WC1N 3HR
        • Great Ormond Street Hospital for Children NHS Foundation Trust
  • Spagna
      • Madrid, Spagna, 28046
        • Hospital Universitario La Paz
      • Seville, Spagna, 41013
        • Hospital Universitario Virgen del Rocío
  • Stati Uniti
    • California
      • Los Angeles, California, Stati Uniti, 90027
        • Childrens Hospital LA
    • Georgia
      • Atlanta, Georgia, Stati Uniti, 30308
        • Hemophilia of Georgia Center for Bleeding & Clotting Disorders
    • Indiana
      • Indianapolis, Indiana, Stati Uniti, 46260
        • Indiana Hemophilia & Thrombosis center
    • Michigan
      • Ann Arbor, Michigan, Stati Uniti, 48109
        • University of Michigan, C.S. Mott Children's Hospital
    • Washington
      • Seattle, Washington, Stati Uniti, 98101
        • Washington Institute for Coagulation
  • Sud Africa
      • Johannesburg, Sud Africa, 2193
        • Charlotte Maxeke Johannesburg Hospital

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Bambino
  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

Criterio di inclusione:

  • Diagnosi di lieve (livello di FVIII tra >5% e
  • Peso ≥3 chilogrammi (kg)
  • Necessità di profilassi basata sulla valutazione dello sperimentatore
  • Un test negativo per l'inibitore (cioè,
  • Nessun inibitore documentato (cioè,
  • Documentazione dei dettagli del trattamento profilattico o episodico con FVIII e del numero di episodi emorragici per almeno le ultime 24 settimane prima dell'arruolamento
  • Adeguata funzionalità ematologica epatica e renale
  • Per le donne in età fertile: accordo a mantenere l'astinenza o usare la contraccezione (come definito nel protocollo) durante il periodo di trattamento e per almeno 24 settimane dopo la dose finale del farmaco in studio

Criteri di esclusione:

  • Disturbi della coagulazione ereditari o acquisiti diversi dall'emofilia congenita lieve o moderata A
  • Storia di abuso di droghe illecite o alcol entro 48 settimane prima dello screening, a giudizio dell'investigatore
  • Trattamento precedente (negli ultimi 12 mesi) o in corso per malattia tromboembolica o segni di malattia tromboembolica
  • Altre condizioni che attualmente possono aumentare il rischio di sanguinamento o trombosi
  • Storia di ipersensibilità clinicamente significativa associata a terapie con anticorpi monoclonali o componenti dell'iniezione di emicizumab
  • Chirurgia pianificata durante la fase della dose di carico di emicizumab (sono consentiti interventi chirurgici nei partecipanti in trattamento con emicizumab dalla settimana 5 in poi)
  • Infezione da HIV nota con conta dei CD4
  • Malattia concomitante, condizione, anomalia significativa nella valutazione dello screening o nei test di laboratorio o trattamento che potrebbe interferire con la conduzione dello studio o che, a parere dello sperimentatore, rappresenterebbe un ulteriore rischio inaccettabile nella somministrazione del farmaco oggetto dello studio al partecipante
  • Ricezione di uno dei seguenti: Un farmaco sperimentale per trattare o ridurre il rischio di sanguinamento emofilico entro 5 emivite dall'ultima somministrazione del farmaco ad eccezione della precedente profilassi con emicizumab; Un farmaco sperimentale non correlato all'emofilia negli ultimi 30 giorni o 5 emivite, a seconda di quale sia più breve; o Qualsiasi altro farmaco sperimentale attualmente somministrato o pianificato per essere somministrato
  • Incapacità di rispettare il protocollo dello studio secondo il parere dello sperimentatore
  • Gravidanza o allattamento o intenzione di rimanere incinta durante lo studio (le donne in età fertile devono avere un risultato negativo del test di gravidanza su siero entro 7 giorni prima dell'inizio del farmaco in studio)

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Emicizumab
I partecipanti con emofilia A lieve e moderata senza inibitori del fattore VIII (FVIII) verranno arruolati per ricevere il regime di dose di carico di emicizumab seguito dalla preferenza del partecipante di uno dei 3 regimi di dose di mantenimento.
Droga: Emicizumab
Quattro dosi di carico di emicizumab 3 milligrammi per chilogrammo di peso corporeo (mg/kg) saranno somministrate per via sottocutanea (SC) una volta alla settimana (QW) per 4 settimane seguite dalla preferenza del partecipante di uno dei tre seguenti regimi di dose di mantenimento SC: 1,5 mg /kg QW, 3 mg/kg una volta ogni 2 settimane (Q2W) o 6 mg/kg una volta ogni 4 settimane (Q4W).
Altri nomi:
  • Hemlibra
  • RO5534262
  • RG6013
  • ACE910

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Tasso di sanguinamento annualizzato basato sul modello per i sanguinamenti trattati
Lasso di tempo: Dal giorno della prima dose di emicizumab ad almeno 52 settimane di trattamento con emicizumab (periodo di efficacia mediano [range, min-max]: 55,64 [8,6-89,9] settimane)
Il numero di sanguinamenti trattati durante il periodo di efficacia è stato stimato come tasso di sanguinamento annualizzato (ABR) utilizzando un modello di regressione binomiale negativo, che tiene conto dei diversi tempi di follow-up. Un'emorragia trattata è stata definita come un'emorragia seguita direttamente da un farmaco per l'emofilia segnalato come "trattamento per l'emorragia". È stata implementata la regola delle 72 ore: due sanguinamenti dello stesso tipo e nella stessa sede anatomica sono stati contati come un sanguinamento se il secondo sanguinamento si è verificato entro 72 ore dall'ultimo trattamento per il primo sanguinamento. Sono stati esclusi i sanguinamenti dovuti a interventi chirurgici/procedure.
Dal giorno della prima dose di emicizumab ad almeno 52 settimane di trattamento con emicizumab (periodo di efficacia mediano [range, min-max]: 55,64 [8,6-89,9] settimane)
Mean Calculated ABR for Treated Bleeds
Lasso di tempo: 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
Lasso di tempo: 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)

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Tasso di sanguinamento annualizzato medio calcolato per i sanguinamenti spontanei trattati
Lasso di tempo: Dal giorno della prima dose di emicizumab ad almeno 52 settimane di trattamento con emicizumab (periodo di efficacia mediano [range, min-max]: 55,64 [8,6-89,9] settimane)
Il numero di sanguinamenti spontanei trattati durante il periodo di efficacia è presentato qui come tasso di sanguinamento annualizzato calcolato (ABR) che è stato annualizzato per ciascun partecipante utilizzando la seguente formula: ABR = (numero di sanguinamenti/numero di giorni durante il periodo di efficacia) x 365,25 . Un'emorragia spontanea trattata è stata definita come un'emorragia trattata (emorragia seguita direttamente da un farmaco per l'emofilia segnalato come "trattamento per emorragia") senza altri fattori contribuenti noti come traumi o procedure/chirurgia. È stata implementata la regola delle 72 ore: due sanguinamenti dello stesso tipo e nella stessa sede anatomica sono stati contati come un sanguinamento se il secondo sanguinamento si è verificato entro 72 ore dall'ultimo trattamento per il primo sanguinamento. Sono stati esclusi i sanguinamenti dovuti a interventi chirurgici/procedure.
Dal giorno della prima dose di emicizumab ad almeno 52 settimane di trattamento con emicizumab (periodo di efficacia mediano [range, min-max]: 55,64 [8,6-89,9] settimane)
Tasso di sanguinamento annualizzato mediano calcolato per sanguinamenti spontanei trattati
Lasso di tempo: Dal giorno della prima dose di emicizumab ad almeno 52 settimane di trattamento con emicizumab (periodo di efficacia mediano [range, min-max]: 55,64 [8,6-89,9] settimane)
Il numero di sanguinamenti spontanei trattati durante il periodo di efficacia è presentato qui come tasso di sanguinamento annualizzato calcolato (ABR) che è stato annualizzato per ciascun partecipante utilizzando la seguente formula: ABR = (numero di sanguinamenti/numero di giorni durante il periodo di efficacia) x 365,25 . Un'emorragia spontanea trattata è stata definita come un'emorragia trattata (emorragia seguita direttamente da un farmaco per l'emofilia segnalato come "trattamento per emorragia") senza altri fattori contribuenti noti come traumi o procedure/chirurgia. È stata implementata la regola delle 72 ore: due sanguinamenti dello stesso tipo e nella stessa sede anatomica sono stati contati come un sanguinamento se il secondo sanguinamento si è verificato entro 72 ore dall'ultimo trattamento per il primo sanguinamento. Sono stati esclusi i sanguinamenti dovuti a interventi chirurgici/procedure.
Dal giorno della prima dose di emicizumab ad almeno 52 settimane di trattamento con emicizumab (periodo di efficacia mediano [range, min-max]: 55,64 [8,6-89,9] settimane)
Percentuale di partecipanti che preferiscono il trattamento con emicizumab SC, il loro precedente trattamento per l'emofilia IV o non hanno alcuna preferenza, come valutato attraverso l'uso del sondaggio sulle preferenze di emicizumab alla settimana 17
Lasso di tempo: Settimana 17
L'Emicizumab Preference Survey è un questionario adatto allo scopo sviluppato dallo sponsor per registrare la preferenza del partecipante per il trattamento con emicizumab sottocutaneo (SC), fattore VIIII (FVIII) per via endovenosa (IV) o nessuna preferenza. Gli intervalli di confidenza al 95% sono stati calcolati utilizzando il metodo Pearson-Clopper.
Settimana 17
Percentuale di caregiver che preferiscono il trattamento con emicizumab SC, il precedente trattamento per l'emofilia IV del loro bambino o non hanno preferenze, come valutato attraverso l'uso del sondaggio sulle preferenze di emicizumab alla settimana 17
Lasso di tempo: Settimana 17
L'Emicizumab Preference Survey è un questionario adatto allo scopo sviluppato dallo sponsor per registrare la preferenza del caregiver per il trattamento del proprio bambino con emicizumab sottocutaneo (SC), fattore VIIII (FVIII) per via endovenosa (IV) o nessuna preferenza. Gli intervalli di confidenza al 95% sono stati calcolati utilizzando il metodo Pearson-Clopper.
Settimana 17
Variazione rispetto al basale della durata media giornaliera del picco di attività nel tempo
Lasso di tempo: Basale (settimane 1-2) e settimane 13 (periodo delle settimane 12-13), 25 (periodo delle settimane 24-25), 37 (periodo delle settimane 36-37) e 49 (periodo delle settimane 48-49)
Per la valutazione dell'attività fisica, i partecipanti di età ≥5 anni sono stati istruiti a indossare il dispositivo di accelerometria dello studio al polso in modo continuo (24 ore al giorno) ogni giorno per i periodi di 2 settimane designati durante lo studio. Un partecipante è stato considerato conforme alle valutazioni dell'attività fisica se indossava il dispositivo dello studio ininterrottamente (≥8 ore/giorno) ogni giorno per almeno 8 giorni di ciascuno dei periodi di 2 settimane designati durante lo studio. Se questo criterio di conformità non è stato raggiunto in un momento specifico, il partecipante non è stato incluso nell'analisi dei periodi di 2 settimane designati in cui la conformità non è stata raggiunta. Le misurazioni giornaliere sono state mediate nel timepoint di 14 giorni. Il conteggio delle attività era una misura dell'accelerazione misurata dal dispositivo. La durata del picco giornaliero di attività è stata definita come la somma dell'attività da moderata a vigorosa al giorno (in minuti).
Basale (settimane 1-2) e settimane 13 (periodo delle settimane 12-13), 25 (periodo delle settimane 24-25), 37 (periodo delle settimane 36-37) e 49 (periodo delle settimane 48-49)
Variazione rispetto al basale nel conteggio giornaliero medio dei passi nel tempo
Lasso di tempo: Basale (settimane 1-2) e settimane 13 (settimane 12-13), 25 (settimane 24-25), 37 (settimane 36-37) e 49 (settimane 48-49)
Per la valutazione dell'attività fisica, i partecipanti di età ≥5 anni sono stati istruiti a indossare il dispositivo di accelerometria dello studio al polso in modo continuo (24 ore al giorno) ogni giorno per i periodi di 2 settimane designati durante lo studio. Un partecipante è stato considerato conforme alle valutazioni dell'attività fisica se indossava il dispositivo dello studio ininterrottamente (≥8 ore/giorno) ogni giorno per almeno 8 giorni di ciascuno dei periodi di 2 settimane designati durante lo studio. Se questo criterio di conformità non è stato raggiunto in un momento specifico, il partecipante non è stato incluso nell'analisi dei periodi di 2 settimane designati in cui la conformità non è stata raggiunta. Le misurazioni giornaliere sono state mediate nel timepoint di 14 giorni. Il conteggio delle attività era una misura dell'accelerazione misurata dal dispositivo.
Basale (settimane 1-2) e settimane 13 (settimane 12-13), 25 (settimane 24-25), 37 (settimane 36-37) e 49 (settimane 48-49)
Model-Based ABR for All Bleeds
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Hoffmann-La Roche

Investigatori

  • Direttore dello studio: Clinical Trials, Hoffmann-La Roche

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

10 febbraio 2020

Completamento primario (Effettivo)

30 ottobre 2021

Completamento dello studio (Effettivo)

19 dicembre 2025

Date di iscrizione allo studio

Primo inviato

7 novembre 2019

Primo inviato che soddisfa i criteri di controllo qualità

7 novembre 2019

Primo Inserito (Effettivo)

12 novembre 2019

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

27 agosto 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

5 agosto 2026

Ultimo verificato

1 agosto 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • BO41423
  • 2019 (Sovvenzione/contratto NIH degli Stati Uniti: Chief Medical Office (CMO) Alberta Health Services)
  • 2023 (Sovvenzione/contratto NIH degli Stati Uniti: GRAMMY Museum Foundation)
  • 2019-002179-32 (Numero EudraCT)
  • 2023-506610-52-00 (Identificatore di registro: EU CT Number)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano IPD

I ricercatori qualificati possono richiedere l'accesso ai dati a livello di singolo paziente attraverso la piattaforma di richiesta (www.vivli.org). Ulteriori dettagli sui criteri di Roche per gli studi ammissibili sono disponibili qui (https://vivli.org/ourmember/roche/).

Per ulteriori dettagli sulla politica globale di Roche sulla condivisione delle informazioni sugli studi clinici e su come richiedere l'accesso ai documenti relativi agli studi clinici, vedere qui (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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