A Clinical Trial of Study Medicine (Marstacimab) in Pediatric Patients With Hemophilia A or Hemophilia B

Официальное название

AN OPEN-LABEL STUDY IN PEDIATRIC (<18 YEARS OF AGE), SEVERE HEMOPHILIA A PARTICIPANTS (COAGULATION FACTOR ACTIVITY <1%) WITH OR WITHOUT INHIBITORS OR MODERATELY SEVERE TO SEVERE HEMOPHILIA B PARTICIPANTS (COAGULATION FACTOR ACTIVITY ≤2%) WITH OR WITHOUT INHIBITORS COMPARING 12 MONTHS OF HISTORICAL STANDARD TREATMENT TO MARSTACIMAB PROPHYLAXIS

Обзор

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called marstacimab) for the potential treatment of hemophilia in pediatric patients. This study will enroll pediatric participants from ages 1 to 17 years in a sequential manner. The study will open enrollment to adolescent participants aged 12 to 17 years first. Then children aged 6 to 11 years will be permitted to enroll. Lastly, children aged 1 to 5 years will be permitted to enroll. This study will enroll participants who: * have severe Hemophilia A or moderately severe to severe Hemophilia B (with or without inhibitors) * have accurate historical records documenting all factor VIII, factor IX, or bypass agent infusions and hemophilia bleed events for at least 1 year prior to entering the study * if a non-inhibitor patient, must be on a stable routine prophylaxis regimen with factor VIII or factor IX replacement products for at least 12 months prior to study entry * if an inhibitor patient, must be on an on-demand bypass treatment regimen during the 12 months prior to study entry All participants in this study will receive marstacimab to use prophylactically. Marstacimab will be given once a week as a subcutaneous (under the skin) shot. The first dose of marstacimab will be given at the study site by the study site staff. During the 12-month treatment period, weekly doses of marstacimab can be given at home, or if preferred, the doses may be given by the study site staff. To help us determine if the study medicine is safe and effective, we will compare participant experiences when they are taking the study medicine to a historical period when they were not. Researchers want to see if the study medicine works to prevent the bleeding episodes commonly experienced by patients with Hemophilia. Participants will be in this study for about 14 months (approximately 1 month in a Screening period, 12 months receiving treatment, and 1 month in a follow-up period) during which they will visit the study site at least 10 times. If preferred, and if local regulations allow it, 2 of the study visits can be completed at the participant's home instead of at the study site. There will also be 6 scheduled telephone calls approximately every 2 months.

Вмешательства

• Препарат marstacimab
  marstacimab

Первичные конечные точки

• Annualized bleeding rate (ABR) of treated bleeding events [Срок оценки: Baseline to end of 12-month treatment period]
• Incidence of adverse events and serious adverse events [Срок оценки: Screening through end of follow-up period (approximately 14 months)]
• Incidence and severity of thrombotic events [Срок оценки: Baseline to end of 12-month treatment period]
• Incidence and severity of thrombotic microangiopathy [Срок оценки: Baseline to end of 12-month treatment period]
• Incidence and severity of disseminated intravascular coagulation/consumption coagulopathy events [Срок оценки: Baseline to end of 12-month treatment period]
• Immunogenicity (incidence of ADA and clinically significant persistent NAb against marstacimab) [Срок оценки: Baseline to end of 12-month treatment period]
• Incidence and severity of injection site reaction [Срок оценки: Baseline to end of 12-month treatment period]
• Incidence of severe hypersensitivity and anaphylactic reactions [Срок оценки: Baseline to end of 12-month treatment period]

Вторичные конечные точки (10)

• Incidence of joint bleeds (treated) [Срок оценки: Baseline to end of 12-month treatment period]
• Incidence of spontaneous bleeds (treated) [Срок оценки: Baseline to end of 12-month treatment period]
• Incidence of target joint bleeds (treated) [Срок оценки: Baseline to end of 12-month treatment period]
• Incidence of total bleeds (treated and untreated) [Срок оценки: Baseline to end of 12-month treatment period]
• Number of target joints [Срок оценки: Baseline to end of 12-month treatment period]
• Change from baseline in joint health as measured by the HJHS for participants ≥4 years of age [Срок оценки: Baseline to end of 12-month treatment period]
• Changes in quality of life measured by Haem-A-QoL/Haemo-QoL (using age-dependent versions for participants ≥8 years of age) [Срок оценки: Baseline to end of 12-month treatment period]
• Changes in quality of life measured by pedHAL (using age-dependent versions for participants ≥4 years of age) [Срок оценки: Baseline to end of 12-month treatment period]
• Changes in quality of life measured by Patient Global Impression of Change - Hemophilia for participants ≥4 years of age [Срок оценки: Baseline to end of 12-month treatment period]
• Changes in quality of life measured by Health Utilities Measure (EQ-5D-Y) for participants ≥4 years of age [Срок оценки: Baseline to end of 12-month treatment period]

Критерии участия

Критерии включения

• Male participants of appropriate age and required minimum weight
• Participants aged 12 to 17 years must be at least 25 kgs at time of consent.
• Participants aged 6 to 11 years must be at least 19 kgs at time of consent.
• Minimum weight requirement for participants aged 1 to 5 years is to be determined.
• Participants with a diagnosis of severe hemophilia A or moderately severe to severe hemophilia B
• Participants must have at least 1 year of diary and/or medical records available in which exogenous FVIII or FIX replacement or bypass agent infusions and hemophilic bleeding episodes were consistently documented over the 12 months prior to the time of consent.

Participants who are enrolled into the Non-Inhibitor Cohort must also meet the following criteria:

• No current detectable inhibitor and no documented history of inhibitors in the 5 years prior to consent
• Must have at least 50 exposure days to FVIII/FIX replacement products
• Must be at least 80% compliant with a stable and effective routine prophylaxis regimen with FVIII/FIX replacement products, for at least 12 months prior to consent

Participants who are enrolled into the Inhibitor Cohort must also meet the following criteria:

• Documentation of current high titer inhibitor (≥5 BU/mL); or current low titer inhibitor (<5 BU/mL) refractory to FVIII or FIX replacement and with FVIII or FIX recovery <60% of expected within previous 12 months prior to the time of consent
• Participants who have documented inhibitors while on factor-replacement therapy but who do not meet the high quantitative inhibitor criteria described in the prior bullet at the time of screening (eg, participant with a previously documented high-titer inhibitor ≥5 BU/mL) and whose condition precludes re-challenge with FVIII or FIX replacement may be considered for eligibility on a case-by-case basis with discussion and agreement from the Pfizer medical monitor.
• Hemophilia A participants with on-demand treatment regimen with ≥12 bleeding episodes or hemophilia B participants with on-demand treatment regimen with ≥8 bleeding episodes (spontaneous or traumatic) necessitating treatment with bypass factor in the 12 months prior to informed consent
• Participants must be on an on-demand bypass treatment regimen during the 12 months prior to informed consent

Критерии исключения

• Known coronary artery, thrombotic, or ischemic disease, or current evidence of congenital or acquired thrombophilic disease such as Anti-thrombin III deficiency, Factor V Leiden mutation, prothrombin 20210 mutation, protein C deficiency, protein S deficiency and antiphospholipid syndrome.
• Known planned surgical procedure during the planned study period
• Known hemostatic defect other than hemophilia A or B
• Abnormal hematology, renal or hepatic function laboratory results at screening
• Other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator
• Individuals with known allergic reaction or hypersensitivity to hamster protein or other components of the study intervention
• Current routine prophylaxis with bypassing agent, non-coagulation non-factor replacement therapy (eg, emicizumab), or any previous treatment with a gene therapy product for treatment of hemophilia
• Participants with inhibitors who are being treated using a prophylaxis treatment regimen with a bypass agent, and, participants who have previously received non-factor-based hemophilia therapy (eg, fitusiran, concizumab, emicizumab) will be considered on a case-by-case basis, only after discussion and agreement between the investigator and the Pfizer medical monitor
• Regular use of immunomodulatory medications (eg, IVIG, routine systemic corticosteroids, rituximab)
• Use of systemic antifibrinolytics, medications that may increase the risk of bleeding, and certain non-steroidal anti-inflammatory drugs within 120 hours of first dose of study intervention and while on study
• Ongoing or planned use of ITI, or prophylaxis with FVIII or FIX replacement at any time after initiation of treatment with study intervention
• Participation in other studies involving investigational drug(s) or investigational vaccine(s) within 30 days (or as determined by local requirements) or 5 half-lives prior to study entry or during study participation
• Previous exposure to marstacimab during participation in other marstacimab clinical studies
• CD4 cell count ≤200/uL if HIV-positive
• Abnormal ECG of clinical relevance that may affect participant safety or interpretation of study results
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their 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) · 4 центра

• Gazi Universitesi Tip Fakultesi Hastanesi Cocuk Hematologi Bolumu — Ankara
• Ege University — Izmir
• Erciyes University Faculty of Medicine Pediatric — Kayseri
• Ondokuz Mayıs Universitesi — Samsun

Китай · 3 центра

• Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology — Ухань
• Tongji Hospital of Tongji Medical College of HUST/Pediatric Hematology Department Pharmacy — Ухань
• Institute of hematology&blood disease hospital — Тяньцзинь

Италия · 3 центра

• Ospedale Pediatrico Bambino Gesù IRCCS — Rome
• Azienda Ospedaliero Universitaria di Parma — Parma
• Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino — Torino

Япония · 3 центра

• Hyogo prefectural Kobe Children's Hospital — Kobe
• Saitama Prefectural Children's Medical Center — Saitama-shi
• Saga University Hospital — Saga

Тайвань · 3 центра

• Changhua Christian Hospital — Changhua County
• Taichung Veterans General Hospital — Taichung
• National Taiwan University Hospital — Taipei

Великобритания · 3 центра

• Royal Victoria Infirmary — Newcastle upon Tyne
• Royal Manchester Children's Hospital — Manchester
• Freeman Hospital — Newcastle upon Tyne

Чехия · 2 центра

• Detska nemocnice FN Brno — Brno
• Motol University Hospital — Prague

Дания · 2 центра

• Rigshospitalet — Copenhagen
• Aarhus Universitetshospital, Skejby — Aarhus N

South Korea · 2 центра

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

Аргентина · 1 центр

• Arbesu Hematología — Mendoza

Австралия · 1 центр

• Murdoch Children's Research Institute — Parkville

Австрия · 1 центр

• Medizinische Universität Wien — Vienna

Канада · 1 центр

• Hamilton Health Sciences - McMaster University Medical Centre — Hamilton

Германия · 1 центр

• Charité Campus Virchow-Klinikum — Berlin

Мексика · 1 центр

• Arké SMO S.A de C.V — Veracruz

Саудовская Аравия · 1 центр

• King Fahad Specialist Hospital — Dammam

Словакия · 1 центр

• Detska fakultna nemocnica Kosice — Košice

Испания · 1 центр

• Hospital Universitario La Paz — Madrid

Идентификаторы

NCT: NCT05611801 · B7841008 · ANTI-TFPI PEDIATRIC STUDY · 2022-500495-65-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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