Clinical trial NCT03191799: A Study to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors
Official title: A Single-Arm, Multicenter Phase IIIB Clinical Trial to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-06-19
Enrollment: 195
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase IIIb, single arm, open-label, multi-center study to evaluate the safety and tolerability of emicizumab in participants with congenital hemophilia A who have documented inhibitors against Factor VIII (FVIII) at enrollment. Approximately 200 participants, aged 12 or older, will be enrolled in this study and are expected to be enrolled at approximately 85 sites globally. Participants will receive an initial weekly dose of prophylactic emicizumab subcutaneously for 4 weeks, followed by a weekly maintenance dose subcutaneously for the remainder of the 2-year treatment period.


Eligibility criteria: Inclusion Criteria:

* As per investigator's judgement, a willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the patient-reported outcome (PRO) questionnaires and bleed diaries through the use of an electronic device or paper
* Aged 12 years or older at the time of informed consent
* Diagnosis of congenital hemophilia A with persistent inhibitors against FVIII
* Documented treatment with bypassing agents or FVIII concentrates in the last 6 months (on-demand or prophylaxis). Prophylaxis needs to be discontinued the latest by a day before starting emicizumab
* Adequate hematologic, hepatic, and renal function
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method with a failure rate of \<1% per year during the treatment period and for at least five elimination half-lives (24 weeks) after the last dose of emicizumab

Exclusion Criteria:

* Inherited or acquired bleeding disorder other than hemophilia A
* Ongoing (or plan to receive during the study) immune tolerance induction (ITI) therapy (prophylaxis regimens with FVIII and/or bypassing agents must be discontinued prior to enrollment). Patients receiving ITI therapy will be eligible following the completion of a 72-hour washout period prior to the first emicizumab administration
* History of illicit drug or alcohol abuse within 12 months prior to screening, as per the investigator's judgment
* High risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA), as per the investigator's judgment
* Previous (in the past 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which antithrombotic treatment is not currently ongoing) or current signs of thromboembolic disease
* Other conditions (e.g., certain autoimmune diseases) that may increase the risk of bleeding or thrombosis
* History of clinically significant hypersensitivity reaction associated with monoclonal antibody therapies or components of the emicizumab injection
* Known human immunodeficiency virus (HIV) infection with CD4 count \<200 cells/μL within 6 months prior to screening
* Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollment or planned use during the study, with the exception of antiretroviral therapy
* Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the investigator or Sponsor, preclude the patient's safe participation in and completion of the study or interpretation of the study results
* Receipt of: Emicizumab in a prior investigational study; An investigational drug to treat or reduce the risk of hemophilic bleeds within five half-lives of last drug administration; A non-hemophilia-related investigational drug within last 30 days or five half-lives, whichever is shorter; or, Any concurrent investigational drug.
* Pregnancy or lactation, or intent to become pregnant during the study
* Positive serum pregnancy test result within 7 days prior to initiation of emicizumab (females only)

Primary outcomes:
measure: Overall Summary of the Number of Participants With Adverse Events, Severity Assessed According to the World Health Organization (WHO) Toxicity Grading Scale
timeFrame: From Baseline until study completion (up to 2 years)
measure: Adverse Events (AEs) Rates Per 100 Patient-Years for All-Grade AEs, Serious AEs, and Grade ≥3 AEs
timeFrame: From Baseline until study completion (up to 2 years)
measure: Number of Participants by Hematology and Biochemistry Laboratory Parameter Test Results as Shifts From the WHO Toxicity Grade at Baseline to the Worst WHO Toxicity Grade Post-Baseline
timeFrame: Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
measure: Change From Baseline in Body Temperature at Specified Timepoints
timeFrame: Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
measure: Change From Baseline in Systolic Blood Pressure at Specified Timepoints
timeFrame: Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
measure: Change From Baseline in Diastolic Blood Pressure at Specified Timepoints
timeFrame: Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
measure: Change From Baseline in Pulse Rate at Specified Timepoints
timeFrame: Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
measure: Change From Baseline in Respiratory Rate at Specified Timepoints
timeFrame: Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
measure: Change From Baseline in Body Weight at Specified Timepoints
timeFrame: Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
Secondary outcomes:
measure: Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Joint Bleeds, Treated Target Joint Bleeds, and Treated Spontaneous Bleeds
timeFrame: From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
measure: Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Joint Bleeds, Treated Target Joint Bleeds, and Treated Spontaneous Bleeds
timeFrame: From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
measure: Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Joint Bleeds, Treated Target Joint Bleeds, and Treated Spontaneous Bleeds
timeFrame: From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
measure: Percentage of Participants by the Categorized Number of Bleeds for Treated Bleeds
timeFrame: From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
measure: Percentage of Participants by the Categorized Number of Bleeds for All Bleeds
timeFrame: From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
measure: Percentage of Participants by the Categorized Number of Bleeds for Treated Spontaneous Bleeds
timeFrame: From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
measure: Percentage of Participants by the Categorized Calculated Annualized Bleed Rates (ABR) for Treated Bleeds
timeFrame: From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
measure: Percentage of Participants by the Categorized Calculated Annualized Bleed Rates (ABR) for All Bleeds
timeFrame: From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
measure: Percentage of Participants by the Categorized Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds
timeFrame: From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
measure: Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Total Score at Specified Timepoints, Adult Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Percentage of Participants With an Improvement From Baseline Greater Than the Responder Threshold for the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Total Score at Specified Timepoints
timeFrame: At 3, 6, 12, and 18 months
measure: Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Physical Health Domain Score at Specified Timepoints, Adult Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Percentage of Participants With an Improvement From Baseline Greater Than the Responder Threshold for the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Physical Health Domain Score at Specified Timepoints
timeFrame: At 3, 6, 12, and 18 months
measure: Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Treatment Domain Score at Specified Timepoints, Adult Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Work and School Domain Score at Specified Timepoints, Adult Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Dealing With Hemophilia Domain Score at Specified Timepoints, Adult Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Feelings Domain Score at Specified Timepoints, Adult Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Family Planning Domain Score at Specified Timepoints, Adult Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Future Domain Score at Specified Timepoints, Adult Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Partnership and Sexuality Domain Score at Specified Timepoints, Adult Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Sports and Leisure Domain Score at Specified Timepoints, Adult Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire View of Yourself Domain Score at Specified Timepoints, Adult Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Total Score at Specified Timepoints, Adolescent Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Percentage of Participants With an Improvement From Baseline Greater Than the Responder Threshold for the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Total Score at Specified Timepoints
timeFrame: At 3, 6, 12, and 18 months
measure: Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Physical Health Domain Score at Specified Timepoints, Adolescent Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Percentage of Participants With an Improvement From Baseline Greater Than the Responder Threshold for the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Physical Health Domain Score at Specified Timepoints
timeFrame: At 3, 6, 12, and 18 months
measure: Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Treatment Domain Score at Specified Timepoints, Adolescent Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Sports and School Domain Score at Specified Timepoints, Adolescent Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Dealing With Hemophilia Domain Score at Specified Timepoints, Adolescent Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Feelings Domain Score at Specified Timepoints, Adolescent Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Family Domain Score at Specified Timepoints, Adolescent Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Friends Domain Score at Specified Timepoints, Adolescent Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Other People Domain Score at Specified Timepoints, Adolescent Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire View of Yourself Domain Score at Specified Timepoints, Adolescent Participants
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the EuroQoL Five-Dimension-Five Levels Questionnaire (EQ-5D-5L) Index Utility Score at Specified Timepoints
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Change From Baseline in the EuroQoL Five-Dimension-Five Levels Questionnaire (EQ-5D-5L) Quality-of-Life Visual Analogue Scale (VAS) Score at Specified Timepoints
timeFrame: Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
measure: Percentage of Participants Who Preferred the New Emicizumab Treatment or the Old Hemophilia Treatment, or Without Treatment Preference, as Assessed by the EmiPref Questionnaire
timeFrame: Month 3
measure: Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) Against Emicizumab at Anytime Post-Baseline
timeFrame: Baseline (Week 1), Week 5, and at 3, 6, 9, 12, and 18 months, and at early termination/study completion (up to 24 months)
measure: Mean Trough Plasma Concentrations of Emicizumab at Specified Timepoints
timeFrame: Pre-dose at Weeks 2, 3, and 5, Months 3, 6, 12, and 18, and at treatment discontinuation (up to 2 years)
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital; Haematology
state: New South Wales
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Curitiba
country: Brazil
facility: Centro de Hematologia E Hemoterapia Do Parana - Hemepar
state: PR
city: Rio de Janeiro
country: Brazil
facility: Instituto Estadual de Hema
state: RJ
city: Campinas
country: Brazil
facility: Hospital das Clinicas - UNICAMP
state: SP
city: Ribeirao Preto
country: Brazil
facility: Faculdade de Medicina de Ribeirão Preto - Universidade de Sao Paulo
state: SP
city: Edmonton
country: Canada
facility: Kaye Edmonton Clinic
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba; Neuro-Oncology
state: Manitoba
city: Hamilton
country: Canada
facility: McMaster University Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Localidad Puente Aranda
country: Colombia
facility: Centro de Atención e Investigación Médica CAIMED S.A.S
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Helsinki
country: Finland
facility: Helsingin yliopistollinen keskussairaala, Meilahden sairaala
city: Berlin
country: Germany
facility: Vivantes Klinikum im Friedrichshain - Landsberger Allee, Angiologie und Hämostaseologie
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn; Institut für Experimentelle Hämatologie und Transfusionsmedizin
city: Frankfurt/M.
country: Germany
facility: Hämophiliezentrum Med. Klinik III/Institut für Transfusionsmedizin; Johann Wolfgang Goethe-Univers.
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig, Innere Medizin, Neurologie, Dermatologie; Zentrum für Hämostaseologie
city: Mörfelden-Walldorf
country: Germany
facility: Hämophilie-Zentrum Rhein Main GmbH
city: München
country: Germany
facility: Klinikum der Universität München, Campus Innenstadt; Hämostaseologische Ambulanz/Hämophiliezentrum
city: Guatemala
country: Guatemala
facility: Oncomedica
city: Budapest
country: Hungary
facility: Magyar Honvédség Egészségügyi Központ; Országos Haemophilia Központ
city: Győr
country: Hungary
facility: Országos Vérellátó Szolgálat - Győri Regionális Vérellátó Központ
city: Pecs
country: Hungary
facility: University of Pecs, I st Dept of Internal Medicine
city: Bengaluru
country: India
facility: St. John's Medical College & Hospital; Department of Medicine
state: Karnataka
city: Mumbai
country: India
facility: King Edward Memorial Hospital and Seth G.S. Medical College; Department of Hematology
state: Maharashtra
city: Mumbai
country: India
facility: Fortis Hospitals Limited
state: Maharashtra
city: Pune
country: India
facility: Sahyadri Speciality Hospital; Hematology & Bone Marrow Unit
state: Maharashtra
city: Vellore
country: India
facility: Christian Medical College & Hospital; Department of Haematology
state: Maharashtra
city: Kolkata
country: India
facility: Nil Ratan Sircar Medical College and Hospital; Department of Hematology
state: WEST Bengal
city: Pune
country: India
facility: Grant Medical Foundation, Ruby Hall Clinic
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center - National Hemophilia Center
city: Napoli
country: Italy
facility: AOU Federico II; Medicina Clinica Chirurgia Centro Emocoaugulopatie e Emofilia
state: Campania
city: Bologna
country: Italy
facility: AOU Policlinico S. Orsola Malpighi; U.O. Angiologia e Malattie della Coagulazione Marino Golinelli
state: Emilia-Romagna
city: Parma
country: Italy
facility: AOU di Parma; Dip Emergenza-Urgenza Centro Riferimento Regionale per l'emofilia
state: Emilia-Romagna
city: Roma
country: Italy
facility: Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol
state: Lazio
city: Milano
country: Italy
facility: IRCCS Ca' Granda Ospedale Maggiore Policlinico; Centro Emofilia e Trombosi "Angelo Bianchi e Bonomi"
state: Lombardia
city: Torino
country: Italy
facility: AO Città Salute e Scienza D-Osp S. G. Battista Molinette; SSCVD Malattie Tromboti e Emorragiche
state: Piemonte
city: Palermo
country: Italy
facility: Azienda Uni Ria Policlinico P. Giaccone ; Divisione Di Ematologia E Trapianto
state: Sicilia
city: Firenze
country: Italy
facility: AOU Careggi; SOD Malattie Emorragiche
state: Toscana
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova; Centro Emofilia
state: Veneto
city: Distrito Federal
country: Mexico
facility: Hospital General de México
state: Mexico CITY (federal District)
city: Mexico City
country: Mexico
facility: CENTRO MEDICO NACIONAL SIGLO XXI; Banco de Sangre
state: Mexico CITY (federal District)
city: Mexico City
country: Mexico
facility: Hospital de Especialidades Centro Medico Nacional La Raza; Haematology
city: Rotterdam
country: Netherlands
facility: Erasmus MC / location Sophia Kinderziekenhuis
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Panama City
country: Panama
facility: Complejo Hospitalario Arnulfo Arias Madrid; Servicio de Hematología
city: Warsaw
country: Poland
facility: Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych
city: Coimbra
country: Portugal
facility: Hospital Geral; Servico de Imuno-Hemoterapia
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria; Servico de Imuno-Hemoterapia; Servico de Imuno-Hemoterapia
city: Porto
country: Portugal
facility: Hospital de Sao Joao; Servico de Imuno-Hemoterapia; Servico de Imuno-Hemoterapia
city: Timisoara
country: Romania
facility: Louis Turcanu Emergency Clinical Hospital for Children; First Pediatric Clinic
city: Barnaul
country: Russian Federation
facility: Regional State Budgetary Institution of Healthcare "Regional Cinilcal Hospital"; Pulmonology
state: Altaj
city: Moscow
country: Russian Federation
facility: Morozov Children's Municipal Clinical Hospital. Haematology department
city: Moscow
country: Russian Federation
facility: "Hematological Scientific Center
city: Saint Petersburg
country: Russian Federation
facility: City Outpatient Clinic #37, City Hemophilia Treatment Center
city: Samara
country: Russian Federation
facility: Samara State Medical University
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Centre; Oncology
city: Barcelona
country: Spain
facility: Hospital Universitario Vall de Hebron; Unidad de Hemofília
city: Madrid
country: Spain
facility: Hospital Universitario la Paz; Servicio de Hematologia
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya; Servicio de Hematologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio; Servicio de Hematologia
city: Valencia
country: Spain
facility: Hospital Universitario la Fe; Servicio de Hematologia
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset; Koagulationscentrum
city: Solna
country: Sweden
facility: Karolinska Universitetssjukhuset; Koagulationsmottagningen
city: Bern
country: Switzerland
facility: Inselspital Bern; Hämatologie und Hämatologisches Zentrallabor
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal London Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary; Non-Malignant Haematology Research
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Foundation Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: