Open-Label Extension Study of Marstacimab in Hemophilia Participants With or Without Inhibitors

Официальное название

AN OPEN-LABEL EXTENSION STUDY TO EVALUATE THE LONG-TERM SAFETY, TOLERABILITY, AND EFFICACY OF MARSTACIMAB PROPHYLAXIS IN SEVERE (COAGULATION FACTOR ACTIVITY <1%) HEMOPHILIA A PARTICIPANTS WITH OR WITHOUT INHIBITORS OR MODERATELY SEVERE TO SEVERE HEMOPHILIA B PARTICIPANTS (COAGULATION FACTOR ACTIVITY ≤2%) WITH OR WITHOUT INHIBITORS

Обзор

Study B7841007 is an open-label extension study to assess the long-term safety, tolerability, and efficacy of prophylaxis treatment with marstacimab in participants who did not require "Early Termination" from the Phase 3 Study B7841005 and from the Phase 3 Study B7841008. Study B7841005: approximately 145 adolescent and adult participants 12 to \<75 years of age with severe hemophilia A or moderately severe to severe hemophilia B (defined as FVIII activity \<1% or FIX activity ≤2%, respectively) with or without inhibitors are expected to be enrolled in Study B7841005 during which they will receive prophylaxis (defined as treatment by SC injection of marstacimab). Study B7841008: this is an ongoing Phase 3, open-label study in pediatric participants \<18 years of age with severe hemophilia A (FVIII Coagulation Factor Activity \<1%) or moderately severe to severe hemophilia B (FIX Coagulation Factor Activity ≤2%). A sequential approach will be used in enrolling at least 100 pediatric participants, at least 20 of which will be aged ≥12 to \<18 years and at least 80 participants will be aged ≥1 to \<12 years. At the start of study B7841008, the dosing and data available in adolescent and adult participants in Study B7841005 supported the initiation of B7841008 study in participants aged ≥12 to \<18 years. Subsequently, additional safety and efficacy data from adolescent participants in Study B7841005 became available for benefit/risk assessment in support of dosing participants aged ≥6 to \<12 years. Based on the positive benefit/risk assessment conducted by both internal Pfizer review and eDMC review, dosing of the ≥6 to \<12 years age group was initiated in June 2023 in B7841008 Study. Data from participants ≥6 years from B7841008 Study and Study B7841005 will support the dosing of participants aged ≥1 to \<6 years. All participants will be provided the prefilled pen (PFP) for administration of marstacimab in the study. Use of the prefilled syringe (PFS) will be permitted at the investigator's discretion for those participants who have difficulty with administration of the PFP. Additionally, participants will be provided the PFS for use in this study in countries where the PFS is anticipated to be the only presentation available commercially. An optional, open-label, single arm, substudy using the PFP was completed in the first 23 participants rolled over from Study B7841005 who agreed to participate in the substudy.

Вмешательства

• Препарат PF-06741086
  For participants aged ≥12 years 300 milligrams(mg) subcutaneous (sc) loading dose followed by 150 mg sq once weekly (qw). 300 mg sc qw is prescribed for participants who meet dose escalation criteria. For participants aged ≥6 to \<12 years is marstacimab 150 mg SC for initial loading dose followed by 75 mg SC QW. 150 mg sc qw is prescribed for participants who meet dose escalation criteria.

Первичные конечные точки

• Number of subject reporting Adverse Events [Срок оценки: Baseline up to 7 years]
• Number of subjects reporting Serious Adverse Events [Срок оценки: Baseline up to 7 years]
• Incidence and severity of thrombotic events [Срок оценки: Baseline up to 7 years]
• Incidence and severity of thrombotic microangiopathy [Срок оценки: Baseline up to 7 years]
• Number of subjects reporting Disseminated intravascular coagulalopathy/consumption coagulopathy [Срок оценки: Baseline up to 7 years]
• Incidence of clinically significant persistent NAb against marstacimab [Срок оценки: Baseline up to 7 years]
• Incidence and severity of injection site reaction [Срок оценки: Baseline up to 7 years]
• Clinically significant changes in vital signs from baseline [Срок оценки: Baseline up to 7 years]
• Incidence of clinically significant laboratory value abnormalities [Срок оценки: Baseline up to 7 years]
• Incidence of severe hypersensitivity and anaphylactic reactions [Срок оценки: Baseline up to 7 years]

Вторичные конечные точки (12)

• Annualized rate of bleeding episodes [Срок оценки: Baseline up to 7 years]
• Total coagulation factor product consumption [Срок оценки: Baseline up to 7 years]
• Incidence of joint bleeds [Срок оценки: Baseline up to 7 years]
• Incidence of spontaneous bleeds [Срок оценки: Baseline up to 7 years]
• Incidence of target joint bleeds [Срок оценки: Baseline up to 7 years]
• Incidence of total bleeds (treated and untreated) [Срок оценки: Baseline up to 7 year]
• Change in joints measured by the HJHS [Срок оценки: Baseline up to 7 years]
• Change in number of target joints per subject from baseline [Срок оценки: Baseline up to 7 years]
• Changes in Health Utilities Measure questionnaire data [Срок оценки: Baseline up to 7 years]
• Changes in Haem-A-QoL questionnaire data for participants ≥17 years of age [Срок оценки: Baseline up to 7 years]
• Changes in Haemo-QoL questionnaire data [Срок оценки: Baseline up to 7 years]
• Total bypass product consumption [Срок оценки: Baseline up to 7 years]

Критерии участия

Критерии включения

• All participants will have a minimum body weight as defined by parent studies
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Participants have successfully completed participation in parent studies, defined as did not require "Early Termination"

Критерии исключения

• Previous or current treatment for or history of coronary artery disease, venous or arterial thrombosis (CTCAE Grade >3), or ischemic disease (except catheter-associated thrombosis)
• Abnormal renal function as defined by eGFR <30 mL.min/1.73 m(2)
• Known planned surgical procedure during the planned study period
• Unstable hepatic function as determined by the Investigator clinical assessment and review of the participant's most recent laboratory results, which would make the participant inappropriate for the study
• For participants known to be HIV+, worsening disease status as determined by the Investigator clinical assessment and review of participant's most recent laboratory results, to include recent locally available CD4 count (if available), which would make the participant inappropriate for the study
• Regular, concomitant therapy with immunomodulatory drugs (eg, IVIG, and routine systemic corticosteroids, rituximab)
• Ongoing or planned use of immune tolerance induction or prophylaxis with FVIII or FIX replacement during the study
• Participation in other study involving investigational drug(s) or investigational vaccine(s) within 30 days or 5 half-lives prior to or during study participation, with the exception of participation in parent studies
• Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the Investigator, and their respective family members

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Turkey (Türkiye) · 13 центров

• Acibadem Adana Hospital — Adana
• Hacettepe University Faculty of Medicine — Ankara
• Hacettepe University Medical Faculty Hospital — Ankara
• Gazi University Medical Faculty — Ankara
• Gazi University Health Research and Application Center Gazi Hospital — Ankara
• Gaziantep University Şahinbey Research and Practice Hospital — Gaziantep
• Istanbul University Oncology Institute — Istanbul
• Istanbul Universitesi Klinik Arastirmalar Mukemmeliyet Uygulama ve Arastirma Merkezi — Istanbul
• … и ещё 5 центров

Китай · 7 центров

• Nanfang Hospital, Southern Medical University — Гуанчжоу
• The Affiliated Hospital of Guizhou Medical University — Guiyang
• Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology — Ухань
• Jiangxi Provincial People's Hospital — Nanchang
• Jiangxi Provincial People's Hospital — Nanchang
• Institute of hematology&blood disease hospital — Тяньцзинь
• Beijing Children's Hospital, Capital Medical University — Пекин

Япония · 7 центров

• Nagoya University Hospital - Transfusion Medicine — Nagoya
• Nagano Children's Hospital — Azumino
• Nara Medical University Hospital — Kashihara
• Saitama Medical University Hospital — Lruma-gun
• Saitama Children's Medical Center — Saitama-shi
• Hiroshima University Hospital — Hiroshima
• Saga University Hospital — Saga

США · 4 центра

• University of Iowa — Iowa City
• Northwell Health HTC — New Hyde Park
• The Feinstein Institutes for Medical Research — Philadelphia
• Washington Institute for Coagulation d/b/a WACBD — Seattle

Гонконг · 4 центра

• The University of Hong Kong (HKU)-Queen Mary Hospital (QMH) — Гонконг
• Prince of Wales Hospital — Гонконг
• Queen Mary Hospital — Гонконг
• The Chinese University of Hong Kong — Ma Liu Shui

Индия · 4 центра

• Nirmal Hospital Pvt Ltd. — Surat
• K.J Somaiya Hospital & Research Centre, Somaiya Ayurvihar Complex — Mumbai
• Sahyadri Super Speciality Hospital — Pune
• Nil Ratan Sircar Medical College and Hospital — Kolkata

Италия · 4 центра

• IRCCS Istituto Giannina Gaslini — Genoa
• Istituto Clinico Humanitas — Rozzano
• AOU Policlinico Umberto I — Roma
• Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico — Milan

Испания · 4 центра

• Hospital Universitario A Coruna — A Coruña
• Hospital Universitario Vall d´Hebron — Barcelona
• Hospital Universitario La Paz — Madrid
• Hospital Universitario Miguel Servet — Zaragoza

Канада · 3 центра

• Stollery Children's Hospital — Edmonton
• Hamilton Health Sciences - McMaster University Medical Centre — Hamilton
• Hamilton Health Sciences - McMaster University Medical Centre — Hamilton

Сербия · 3 центра

• Institute for Mother and Child healthcare "Dr Vukan Cupic" — Belgrade
• Clinical Center Nis — Niš
• Clinical Center Nis — Niš

ЮАР · 3 центра

• Worthwhile Clinical Trials — Benoni
• Charlotte Maxeke Johannesburg Academic Hospital — Johannesburg
• WITS Health Consortium — Johannesburg

South Korea · 3 центра

• Kyung Hee University Hospital at Gangdong — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• Kyungpook National University Hospital — Daegu

Великобритания · 3 центра

• Royal Victoria Infirmary — Newcastle upon Tyne
• Guy's & St Thomas' NHS Foundation Trust — London
• Guy's & St Thomas' NHS Foundation Trust, St Thomas' Hospital — London

Словакия · 2 центра

• Detska fakultna nemocnica Kosice — Košice
• Univerzitna nemocnica Martin — Martin

Тайвань · 2 центра

• ChangHua Christian Hospital — Changhua
• Taichung Veterans General Hospital — Taichung

Аргентина · 1 центр

• Arbesu Hematología — Mendoza

Австралия · 1 центр

• Royal Children's Hospital — Melbourne

Бразилия · 1 центр

• HEMOES — Vitória

Хорватия · 1 центр

• Klinicki bolnicki centar Zagreb — Zagreb

Дания · 1 центр

• Aarhus Universitetshospital, Skejby — Aarhus

Франция · 1 центр

• Hôpital Universitaire Necker Enfants Malades — Paris

Израиль · 1 центр

• Sheba Medical Center — Ramat Gan

Мексика · 1 центр

• Centro Multidisciplinario para el Desarrollo Especializado de la Investigacion Clinica en — Mérida

Oman · 1 центр

• Sultan Qaboos University Hospital — Muscat

Идентификаторы

NCT: NCT05145127 · B7841007 · PHASE 3 ANTI-TFPI OLE · 2022-500470-33-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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