A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants With Inhibitors
NCT ID: NCT02622321
Last Updated: 2021-06-24
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
113 participants
INTERVENTIONAL
2015-11-18
2020-12-01
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A: 1.5 mg/kg Emicizumab QW
Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm A started to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 milligrams per kilogram (mg/kg) once a week (QW) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.
Emicizumab
Emicizumab will be administered at a loading dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. After at least 24 weeks on prophylactic emicizumab, individuals who experience suboptimal bleeding control on emicizumab (according to protocol-defined criteria) will have the opportunity to increase their dose to 3 mg/kg weekly.
rFVIIa
Participants will continue to receive rFVIIa.
aPCC
Participants will continue to receive aPCC.
Arm B (Control): No Prophylaxis, Then Emicizumab
Participants who were receiving episodic treatment with bypassing agents prior to study entry and were randomized to study Arm B continued with their prior episodic treatment regimen for the first 24 weeks of the study; they did not receive emicizumab prophylaxis during that time. After completing at least 24 weeks on study, participants in Arm B were allowed to switch to emicizumab prophylaxis (as described for Arm A) up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.
Emicizumab
Emicizumab will be administered at a loading dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. After at least 24 weeks on prophylactic emicizumab, individuals who experience suboptimal bleeding control on emicizumab (according to protocol-defined criteria) will have the opportunity to increase their dose to 3 mg/kg weekly.
rFVIIa
Participants will continue to receive rFVIIa.
aPCC
Participants will continue to receive aPCC.
Arm C: 1.5 mg/kg Emicizumab QW
Participants who were receiving prophylactic bypassing agents prior to study entry were enrolled in Arm C to receive prophylactic emicizumab. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.
Emicizumab
Emicizumab will be administered at a loading dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. After at least 24 weeks on prophylactic emicizumab, individuals who experience suboptimal bleeding control on emicizumab (according to protocol-defined criteria) will have the opportunity to increase their dose to 3 mg/kg weekly.
rFVIIa
Participants will continue to receive rFVIIa.
aPCC
Participants will continue to receive aPCC.
Arm D: 1.5 mg/kg Emicizumab QW
Participants who were either: 1) Receiving episodic bypassing agents prior to study entry but were unable to enroll in Arms A or B; or 2) Receiving bypassing agent prophylaxis prior to study entry but were unable to enroll in Arm C, were enrolled in Arm D to receive emicizumab prophylaxis. Emicizumab was administered at a loading dose of 3 mg/kg QW SC for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg emicizumab QW SC up to the end of study. Participants continued to receive bypassing agent therapy to treat any breakthrough bleeds.
Emicizumab
Emicizumab will be administered at a loading dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. After at least 24 weeks on prophylactic emicizumab, individuals who experience suboptimal bleeding control on emicizumab (according to protocol-defined criteria) will have the opportunity to increase their dose to 3 mg/kg weekly.
rFVIIa
Participants will continue to receive rFVIIa.
aPCC
Participants will continue to receive aPCC.
Interventions
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Emicizumab
Emicizumab will be administered at a loading dose of 3 milligrams per kilogram per week (mg/kg/week) subcutaneously (SC) for the first 4 weeks followed by a maintenance dose of 1.5 mg/kg/week SC up to the end of study. After at least 24 weeks on prophylactic emicizumab, individuals who experience suboptimal bleeding control on emicizumab (according to protocol-defined criteria) will have the opportunity to increase their dose to 3 mg/kg weekly.
rFVIIa
Participants will continue to receive rFVIIa.
aPCC
Participants will continue to receive aPCC.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor ( that is \[i.e.\], \>/= 5 Bethesda Units \[BU\])
* Documentation of treatment with episodic or prophylactic bypassing agents for at least the last 24 weeks
* \>/= 6 bleeds in the last 24 weeks prior to screening (if on an episodic bypassing agent regimen) or \>/=2 bleeds in the last 24 weeks prior to screening (if on a prophylactic bypassing agent regimen)
* Adequate hematologic, hepatic and renal function
* For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use single or combined highly effective contraceptive methods
Exclusion Criteria
* Participants with ongoing (or plan to receive during the study) immune tolerance induction therapy or prophylaxis with Factor VIII (FVIII), with the exception of participants who have received a treatment regimen of FVIII prophylaxis with concurrent bypassing agent prophylaxis
* 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
* Participants with other conditions (for example \[e.g.\], certain autoimmune diseases) that may increase the risk of bleeding or thrombosis
* History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
* Known human immunodeficiency virus (HIV) infection with cluster of differentiation 4 (CD4) count \< 200 cells per microliter (cells/mcL) within 24 weeks prior to screening
* Use of systemic immunomodulators (e.g., interferon or rituximab) at enrolment or planned use during the study, with the exception of antiretroviral therapy
* Participants who are at high risk for thrombotic microangiopathy (TMA; e.g., have a previous medical or family history of TMA), in the investigator's judgment
* 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 participant's safe participation in and completion of the study or interpretation of the study results
* Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study
* Receipt of emicizumab in a prior investigational study; An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration; A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter; An investigational drug concurrently
* Unwillingness to use highly effective contraception methods for the specified duration in the protocol (females only, unless required otherwise by the local health authority)
* Clinically significant abnormality on screening evaluations or laboratory tests that, in the opinion of the investigator, may pose an additional risk in administering study drug to the participant
* Pregnancy or lactation, or intent to become pregnant during the study
12 Years
ALL
No
Sponsors
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Chugai Pharmaceutical
INDUSTRY
Hoffmann-La Roche
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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Children's Hospital Los Angeles
Los Angeles, California, United States
Santa Monica Oncology Center
Santa Monica, California, United States
University of Colorado Denver, Children's Hospital
Aurora, Colorado, United States
Winship Cancer Institute
Atlanta, Georgia, United States
Boston Childrens Hospital
Boston, Massachusetts, United States
Children's Hospital of Michigan; Pediatrics
Detroit, Michigan, United States
Cornell Univ Medical College; Hematology-Oncolog
New York, New York, United States
Oregon Health & Science Uni ; Dept of Pediatrics
Portland, Oregon, United States
Pennsylvania State Hershey Medical Center; Division of Hematology/Oncology, H046
Hershey, Pennsylvania, United States
Univ of TX Health Science Ctr; Gulf States Hemo and Throm Ctr
Houston, Texas, United States
Bloodworks Northwest (formerly Puget Sound Blood Center); Hemophilia
Seattle, Washington, United States
Royal Prince Alfred Hospital; Haematology
Camperdown, New South Wales, Australia
The Alfred Hospital, Melbourne; Thrombosis and Haemostasis Unit
Melbourne, Victoria, Australia
ICIC
San José, , Costa Rica
Hopital Cardio-vasculaire Louis Pradel; Hemostase clinique
Bron, , France
CH de Bicetre; Centre de Traitement d' Hemophilie
Le Kremlin-Bicêtre, , France
Hopital Cardiologique; Hematologie B
Lille, , France
Groupe Hospitalier Necker Enfants Malades
Paris, , France
Universitätsklinikum Bonn; Institut für Experimentelle Hämatologie und Transfusionsmedizin
Bonn, , Germany
CTC North GmbH & Co. KG am Universitätsklinikum Hamburg-Eppendorf
Hamburg, , Germany
Hämophilie-Zentrum Rhein Main GmbH
Mörfelden-Walldorf, , Germany
IRCCS Ca' Granda Ospedale Maggiore Policlinico; Centro Emofilia e Trombosi "Angelo Bianchi e Bonomi"
Milan, Lombardy, Italy
AOU Careggi; SOD Malattie Emorragiche
Florence, Tuscany, Italy
Nagoya University Hospital
Aichi, , Japan
Hiroshima University Hospital
Hiroshima, , Japan
Hyogo College of Medicine Hospital
Hyōgo, , Japan
St. Marianna University School of Medicine Hospital
Kanagawa, , Japan
Hospital of the University of Occupational and Environmental Health,Japan
Kitakyushu-shi, , Japan
Nara Medical University Hospital
Nara, , Japan
Tokyo Medical University Hospital
Tokyo, , Japan
Auckland City Hospital; Auckland Haemophilia Centre
Auckland, , New Zealand
Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii
Gdansk, , Poland
SPSK Nr1 Klinika Hematoo&Transpl.Szpiku
Lublin, , Poland
ALVAMED Lekarskie Gabinety Specjalistyczne
Poznan, , Poland
Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych
Warsaw, , Poland
Charlotte Maxeke Johannesburg Hospital; Haemophilia Comprehensive Care Center
Johannesburg, , South Africa
Severance Hospital
Seoul, , South Korea
Hospital Universitario la Paz; Servicio de Hematologia
Madrid, , Spain
Hospital Universitario Virgen del Rocio; Servicio de Hematologia
Seville, , Spain
Hospital Universitario la Fe; Servicio de Hematologia
Valencia, , Spain
National Taiwan Uni Hospital
Taipei, , Taiwan
Cardiff and Vale NHS Trust
Cardiff, , United Kingdom
St Thomas' Hospital; Haemostasis & Thromboisis Centre
London, , United Kingdom
Oxford University Hospitals NHS Trust - Churchill Hospital
Oxford, , United Kingdom
Countries
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References
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Kruse-Jarres R, Peyvandi F, Oldenburg J, Chang T, Chebon S, Doral MY, Croteau SE, Lambert T, Kempton CL, Pipe SW, Ko RH, Trzaskoma B, Dhalluin C, Bienz NS, Niggli M, Lehle M, Paz-Priel I, Young G, Jimenez-Yuste V. Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies. Blood Adv. 2022 Dec 27;6(24):6140-6150. doi: 10.1182/bloodadvances.2022007458.
Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, Santagostino E, Kruse-Jarres R, Negrier C, Kessler C, Valente N, Asikanius E, Levy GG, Windyga J, Shima M. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med. 2017 Aug 31;377(9):809-818. doi: 10.1056/NEJMoa1703068. Epub 2017 Jul 10.
Other Identifiers
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2015-002866-21
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
BH29884
Identifier Type: -
Identifier Source: org_study_id
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