A Study to Assess the Efficacy and Safety of Emicizumab in Participants With Type 3 Von Willebrand Disease

Официальное название

A Phase III, Multicenter, Open-Label Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Emicizumab Prophylaxis in Patients With Type 3 Von Willebrand Disease

Обзор

This is a Phase III, multicenter, open-label clinical study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab prophylaxis in participants aged 1 month and above, who have been diagnosed with Type 3 von Willebrand disease (VWD). Participants on prior standard of care (SOC) on-demand therapy will be assessed via a randomized comparison (Arm A - emicizumab prophylaxis and Arm B - continuation of SOC on-demand therapy), while participants on prior SOC prophylactic therapy (Arm C - emicizumab prophylaxis) will be assessed via intra-participant analysis with data obtained from the preceding non-interventional study (NIS), WP45335 (NCT06883240).

Вмешательства

• Препарат Emicizumab
  Participants will receive emicizumab 3 milligrams per kilogram (mg/kg) subcutaneous (SC) injections every week (QW) for the first 4 weeks as loading doses, followed by maintenance doses of emicizumab 3 mg/kg SC once every 2 weeks (Q2W). During the extension period, participants may remain on maintenance dose of emicizumab 3 mg/kg Q2W, or change their emicizumab maintenance regimen to 1.5 mg/kg once every week (QW) or 6 mg/kg once every 4 weeks (Q4W), if they prefer and if agreed by the investig
• Препарат von Willebrand Factor (VWF) Concentrates
  Used according to local labeling or local treatment guidelines.
• Препарат Factor VIII (FVIII) Concentrates
  Used according to local labeling or local treatment guidelines.
• Препарат von Willebrand Factor (VWF) and Factor VIII (FVIII) Concentrates
  Used according to local labeling or local treatment guidelines.
• Препарат Bypassing Agents
  Used according to local labeling or local treatment guidelines.

Первичные конечные точки

• Annualized Bleed Rate (ABR) for Treated Bleeds in the Randomized Arms [Срок оценки: From Baseline to at least 24 weeks]

Вторичные конечные точки (12)

• ABR for All Bleeds in the Randomized Arms [Срок оценки: From Baseline to at least 24 weeks]
• ABR for Treated Spontaneous Bleeds in the Randomized Arms [Срок оценки: From Baseline to at least 24 weeks]
• ABR for Treated Joint Bleeds in the Randomized Arms [Срок оценки: From Baseline to at least 24 weeks]
• Intra-Participant Comparison of the ABR for Treated Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding Non-Interventional Study (NIS) WP45335 [Срок оценки: From Baseline to at least 24 weeks]
• Intra-Participant Comparison of the ABR for All Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335 [Срок оценки: From Baseline to at least 24 weeks]
• Intra-Participant Comparison of the ABR for Treated Spontaneous Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335 [Срок оценки: From Baseline to at least 24 weeks]
• Intra-Participant Comparison of the ABR for Treated Joint Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335 [Срок оценки: From Baseline to at least 24 weeks]
• Incidence and Severity of Adverse Events, with Severity Determined According to the World Health Organization (WHO) Toxicity Grading Scale [Срок оценки: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)]
• Incidence and Severity of Thromboembolic Events [Срок оценки: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)]
• Incidence and Severity of Thrombotic Microangiopathy Events [Срок оценки: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)]
• Incidence and Severity of Injection-Site Reactions [Срок оценки: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)]
• Incidence of Adverse Events Leading to Drug Discontinuation [Срок оценки: From first dose of study treatment until 24 weeks after final dose of study treatment (up to 3 years, 11 months)]

Критерии участия

Критерии включения

• Confirmed diagnosis of Type 3 von Willebrand disease (VWD), based on medical records
• Preexisting medical record verifying the status of von Willebrand factor (VWF) inhibitor (positive or negative, including titer if available)
• Adequate hematologic, hepatic, and renal function
• For participants of childbearing potential: agreement to remain abstinent or adhere to the contraception requirements

Additional Inclusion Criteria for Arms A and B:

• Age ≥1 month at the time of signing Informed Consent/Assent Form
• Documented previous use of on-demand therapy with intermittent (less than once a week) on-demand SOC therapy for VWD
• Having ≥2 treated bleeds (except menstrual bleeds) with factor concentrate within 24 weeks prior to enrollment

Additional Inclusion Criteria for Arm C:

• Age ≥2 years at the time of signing Informed Consent/Assent Form
• Documented and confirmed previous use of SOC prophylactic therapy for VWD (1-3 times weekly, as per prescribed dose) as described in the eligibility of Study WP45335
• Have completed all study requirements as defined in the WP45335 protocol for at least 24 weeks

Критерии исключения

• Inherited or acquired bleeding disorder other than Congenital Type 3 VWD
• History of gastrointestinal bleeding within 18 months prior to enrollment, or any previous diagnosis of angiodysplasia
• History of intracranial hemorrhage
• Previous or current treatment for thromboembolic disease or signs of thromboembolic disease
• Other conditions (e.g., certain autoimmune diseases) that may increase risk of bleeding or thrombosis
• History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
• Use of systemic immunomodulators (e.g., interferon) at enrollment or planned use during the study, with the exception of anti-retroviral therapy

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 5 центров

• UC Davis — Sacramento
• University of Florida — Gainesville
• University of Minnesota Medical Center — Minneapolis
• Washington University School of Medicine — St Louis
• Virginia Commonwealth University — Richmond

Германия · 3 центра

• Universitätsklinikum Bonn — Bonn
• Gerinnungszentrum Rhein-Ruhr;Gerinnungsambulanz — Duisburg
• Hämophiliezentrum Med. Klinik III/Institut für Transfusionsmedizin — Frankfurt/M.

Италия · 3 центра

• Universita' Degli Studi La Sapienza-Ist.Di Ematologia — Rome
• IRCCS Ca' Granda Ospedale Maggiore Policlinico — Milan
• AOU Careggi — Florence

Великобритания · 3 центра

• St Thomas' Hospital — London
• Great Ormond Street Hospital — London
• Manchester Royal Infirmary — Manchester

Канада · 2 центра

• The Hospital for Sick Children — Toronto
• McGill University Health Center — Montreal

Франция · 2 центра

• Hopital Claude Huriez - CHU Lille — Lille
• Groupe Hospitalier Necker Enfants Malades — Paris

Япония · 2 центра

• Kurume University Hospital — Fukuoka
• Nagoya University Hospital — Nagoya

Испания · 2 центра

• Hospital Universitario la Paz — Madrid
• Hospital Universitario Virgen del Rocio — Seville

Бельгия · 1 центр

• UZ Leuven Gasthuisberg — Leuven

Колумбия · 1 центр

• IPS SURA Industriales Medellín — Medellín

Нидерланды · 1 центр

• Erasmus MC — Rotterdam

Польша · 1 центр

• Instytut Hematologii i Transfuzjologii — Warsaw

ЮАР · 1 центр

• Charlotte Maxeke Johannesburg Academic Hospital — Johannesburg

Швеция · 1 центр

• Sahlgrenska Universitetssjukhuset — Gothenburg

Идентификаторы

NCT: NCT06998524 · WP45338 · 2024-515622-80-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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