A Study to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors

NCT ID: NCT03191799

Last Updated: 2021-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 195 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-05
• Study Completion Date: 2020-11-19

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.

Conditions

Hemophilia A

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1.5 mg/kg Emicizumab QW

Participants will receive initial weekly doses of prophylactic emicizumab subcutaneously for 4 weeks, followed by maintenance doses consisting of half the initial dose, administered subcutaneously for the remainder of the 2-year treatment period

Group Type: EXPERIMENTAL

Emicizumab

Intervention Type: DRUG

Initial dosing will be 3 mg/kg/week subcutaneously for 4 weeks; Maintenance dosing will follow at 1.5 mg/kg/week subcutaneously for the remainder of the 2-year treatment period

Interventions

Emicizumab

Initial dosing will be 3 mg/kg/week subcutaneously for 4 weeks; Maintenance dosing will follow at 1.5 mg/kg/week subcutaneously for the remainder of the 2-year treatment period

Intervention Type: DRUG

Other Intervention Names

Hemlibra; RO5534262; ACE910

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)

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Royal Prince Alfred Hospital; Haematology

Camperdown, New South Wales, Australia

Alfred Hospital

Melbourne, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

UZ Leuven Gasthuisberg

Leuven, , Belgium

Centro de Hematologia E Hemoterapia Do Parana - Hemepar

Curitiba, Paraná, Brazil

Instituto Estadual de Hema

Rio de Janeiro, Rio de Janeiro, Brazil

Hospital das Clinicas - UNICAMP

Campinas, São Paulo, Brazil

Faculdade de Medicina de Ribeirão Preto - Universidade de Sao Paulo

Ribeirão Preto, São Paulo, Brazil

Kaye Edmonton Clinic

Edmonton, Alberta, Canada

CancerCare Manitoba; Neuro-Oncology

Winnipeg, Manitoba, Canada

McMaster University Health Sciences Center

Hamilton, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Centro de Atención e Investigación Médica CAIMED S.A.S

Localidad Puente Aranda, , Colombia

Hospital Pablo Tobon Uribe

Medellín, , Colombia

Helsingin yliopistollinen keskussairaala, Meilahden sairaala

Helsinki, , Finland

Vivantes Klinikum im Friedrichshain - Landsberger Allee, Angiologie und Hämostaseologie

Berlin, , Germany

Universitätsklinikum Bonn; Institut für Experimentelle Hämatologie und Transfusionsmedizin

Bonn, , Germany

Hämophiliezentrum Med. Klinik III/Institut für Transfusionsmedizin; Johann Wolfgang Goethe-Univers.

Frankfurt/M., , Germany

Universitätsklinikum Leipzig, Innere Medizin, Neurologie, Dermatologie; Zentrum für Hämostaseologie

Leipzig, , Germany

Hämophilie-Zentrum Rhein Main GmbH

Mörfelden-Walldorf, , Germany

Klinikum der Universität München, Campus Innenstadt; Hämostaseologische Ambulanz/Hämophiliezentrum

München, , Germany

Oncomedica

Guatemala City, , Guatemala

Magyar Honvédség Egészségügyi Központ; Országos Haemophilia Központ

Budapest, , Hungary

Országos Vérellátó Szolgálat - Győri Regionális Vérellátó Központ

Győr, , Hungary

University of Pecs, I st Dept of Internal Medicine

Pécs, , Hungary

St. John's Medical College & Hospital; Department of Medicine

Bengaluru, Karnataka, India

King Edward Memorial Hospital and Seth G.S. Medical College; Department of Hematology

Mumbai, Maharashtra, India

Fortis Hospitals Limited

Mumbai, Maharashtra, India

Sahyadri Speciality Hospital; Hematology & Bone Marrow Unit

Pune, Maharashtra, India

Christian Medical College & Hospital; Department of Haematology

Vellore, Maharashtra, India

Nil Ratan Sircar Medical College and Hospital; Department of Hematology

Kolkata, West Bengal, India

Grant Medical Foundation, Ruby Hall Clinic

Pune, , India

Sheba Medical Center - National Hemophilia Center

Tel Litwinsky, , Israel

AOU Federico II; Medicina Clinica Chirurgia Centro Emocoaugulopatie e Emofilia

Napoli, Campania, Italy

AOU Policlinico S. Orsola Malpighi; U.O. Angiologia e Malattie della Coagulazione Marino Golinelli

Bologna, Emilia-Romagna, Italy

AOU di Parma; Dip Emergenza-Urgenza Centro Riferimento Regionale per l'emofilia

Parma, Emilia-Romagna, Italy

Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol

Rome, Lazio, Italy

IRCCS Ca' Granda Ospedale Maggiore Policlinico; Centro Emofilia e Trombosi "Angelo Bianchi e Bonomi"

Milan, Lombardy, Italy

AO Città Salute e Scienza D-Osp S. G. Battista Molinette; SSCVD Malattie Tromboti e Emorragiche

Turin, Piedmont, Italy

Azienda Uni Ria Policlinico P. Giaccone ; Divisione Di Ematologia E Trapianto

Palermo, Sicily, Italy

AOU Careggi; SOD Malattie Emorragiche

Florence, Tuscany, Italy

Azienda Ospedaliera di Padova; Centro Emofilia

Padua, Veneto, Italy

Hospital General de México

Distrito Federal, Mexico CITY (federal District), Mexico

CENTRO MEDICO NACIONAL SIGLO XXI; Banco de Sangre

Mexico City, Mexico CITY (federal District), Mexico

Hospital de Especialidades Centro Medico Nacional La Raza; Haematology

Mexico City, , Mexico

Erasmus MC / location Sophia Kinderziekenhuis

Rotterdam, , Netherlands

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Complejo Hospitalario Arnulfo Arias Madrid; Servicio de Hematología

Panama City, , Panama

Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych

Warsaw, , Poland

Hospital Geral; Servico de Imuno-Hemoterapia

Coimbra, , Portugal

Hospital de Santa Maria; Servico de Imuno-Hemoterapia; Servico de Imuno-Hemoterapia

Lisbon, , Portugal

Hospital de Sao Joao; Servico de Imuno-Hemoterapia; Servico de Imuno-Hemoterapia

Porto, , Portugal

Louis Turcanu Emergency Clinical Hospital for Children; First Pediatric Clinic

Timișoara, , Romania

Regional State Budgetary Institution of Healthcare "Regional Cinilcal Hospital"; Pulmonology

Barnaul, Altayskiy Kray, Russia

Morozov Children's Municipal Clinical Hospital. Haematology department

Moscow, , Russia

"Hematological Scientific Center

Moscow, , Russia

City Outpatient Clinic #37, City Hemophilia Treatment Center

Saint Petersburg, , Russia

Samara State Medical University

Samara, , Russia

King Faisal Specialist Hospital & Research Centre; Oncology

Riyadh, , Saudi Arabia

Hospital Universitario Vall de Hebron; Unidad de Hemofília

Barcelona, , Spain

Hospital Universitario la Paz; Servicio de Hematologia

Madrid, , Spain

Hospital Regional Universitario Carlos Haya; Servicio de Hematologia

Málaga, , Spain

Hospital Universitario Virgen del Rocio; Servicio de Hematologia

Seville, , Spain

Hospital Universitario la Fe; Servicio de Hematologia

Valencia, , Spain

Sahlgrenska Universitetssjukhuset; Koagulationscentrum

Gothenburg, , Sweden

Karolinska Universitetssjukhuset; Koagulationsmottagningen

Solna, , Sweden

Inselspital Bern; Hämatologie und Hämatologisches Zentrallabor

Bern, , Switzerland

University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

The Royal London Hospital

London, , United Kingdom

Royal Free Hospital

London, , United Kingdom

Royal Victoria Infirmary; Non-Malignant Haematology Research

Newcastle upon Tyne, , United Kingdom

Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, , United Kingdom

Countries

Australia; Belgium; Brazil; Canada; Colombia; Finland; Germany; Guatemala; Hungary; India; Israel; Italy; Mexico; Netherlands; Panama; Poland; Portugal; Romania; Russia; Saudi Arabia; Spain; Sweden; Switzerland; United Kingdom

References

Castaman G, Peyvandi F, Kremer Hovinga JA, Schutgens REG, Robson S, Moreno K, Jimenez-Yuste V. Surgical Experience from the STASEY Study of Emicizumab Prophylaxis in People with Hemophilia A with Factor VIII Inhibitors. TH Open. 2024 Jan 12;8(1):e42-e54. doi: 10.1055/s-0043-1777766. eCollection 2024 Jan.

Reference Type: DERIVED

PMID: 38222041 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-004366-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO39129

Identifier Type: -

Identifier Source: org_study_id