Resumen

El propósito de este ensayo clínico es conocer la seguridad y los efectos del medicamento del estudio (llamado marstacimab) para el posible tratamiento de la hemofilia en pacientes pediátricos. Este estudio incorporará participantes pediátricos de 1 a 17 años de manera secuencial. El estudio abrirá primero la incorporación a participantes adolescentes de 12 a 17 años. Luego se permitirá la incorporación de niños de 6 a 11 años. Por último, se permitirá la incorporación de niños de 1 a 5 años. Este estudio incorporará participantes que: * Tengan Hemofilia A grave o Hemofilia B de moderadamente grave a grave (con o sin inhibidores). * Tengan registros históricos precisos que documenten todas las infusiones de factor VIII, factor IX o agente de bypass y los episodios hemorrágicos de hemofilia durante al menos 1 año antes de entrar en el estudio. * Si son pacientes sin inhibidores, deben seguir un régimen de profilaxis habitual estable con productos de reemplazo de factor VIII o factor IX durante al menos 12 meses previos a la entrada en el estudio. * Si son pacientes con inhibidores, deben seguir un régimen de tratamiento a demanda con agente de bypass durante los 12 meses previos a la entrada en el estudio. Todos los participantes en este estudio recibirán marstacimab como profilaxis. Marstacimab se administrará una vez por semana como inyección subcutánea (debajo de la piel). La primera dosis de marstacimab se administrará en el centro del estudio por el personal del mismo. Durante el período de tratamiento de 12 meses, las dosis semanales de marstacimab pueden administrarse en casa o, si se prefiere, por el personal del centro del estudio. Para ayudarnos a determinar si el medicamento del estudio es seguro y eficaz, compararemos las experiencias de los participantes cuando están tomando el medicamento del estudio con un período histórico en el que no lo estaban tomando. Los investigadores desean comprobar si el medicamento del estudio funciona para prevenir los episodios hemorrágicos que suelen experimentar los pacientes con hemofilia. Los participantes estarán en este estudio durante aproximadamente 14 meses (aproximadamente 1 mes en un período de Selección, 12 meses recibiendo tratamiento y 1 mes en un período de seguimiento) durante los cuales visitarán el centro del estudio al menos 10 veces. Si se prefiere y las normativas locales lo permiten, 2 de las visitas del estudio pueden realizarse en el domicilio del participante en lugar de en el centro del estudio. También habrá 6 llamadas telefónicas programadas aproximadamente cada 2 meses.

Elegibilidad

Edad mínima: 1 YearEdad máxima: 17 YearsSexo: MALE

Criterios de inclusión

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

Criterios de exclusión

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

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

marstacimab

Ubicaciones

Arbesu Hematología

Patrocinadores

Contactos

Pfizer CT.gov Call Center