Descripción del proyecto
Nuevo ensayo para tratar una enfermedad rara
La fibrodisplasia osificante progresiva (FOP), identificada por primera vez en el siglo XVIII, es una enfermedad hereditaria del tejido conjuntivo. La FOP, causada por una mutación en el gen ACVR1 y caracterizada por la osificación heterotópica progresiva del tejido fibroso, tiene como resultado la parálisis. Las personas que la padecen tienen una esperanza de vida de cuarenta años. Aunque en la actualidad no hay ningún tratamiento aprobado, el proyecto STOPFOP, financiado con fondos europeos, estudiará si el fármaco en proceso de investigación AZD0530, también conocido como saracatinib, podría utilizarse para tratar la FOP. El estudio se llevará a cabo en tres centros expertos en FOP en Alemania, los Países Bajos y el Reino Unido. El objetivo general del proyecto es ofrecer una prueba de concepto de que AZD0530 es un fármaco eficaz en el tratamiento de pacientes con FOP.
Objetivo
Fibrodysplasia ossificans progressiva (FOP) is a rare, disabling and life-shortening congenital syndrome for which no effective therapies exist. Repurposing of AZD0530 (saracatinib, AstraZeneca) would be an ideal solution for de-risking early clinical studies. Using existing assets and investments, this may allow more affordable pricing once an indication is approved. Ectopic bone is formed in soft tissues due to activating mutations in the bone morphogenetic protein receptor kinase ALK2/ACVR1, leading to progressive contractures and early death. Preclinical studies showed AZD0530, previously unexplored in FOP, to be a potent (5nM) inhibitor of ALK2 kinase and ALK2-R206H-mediated neofunction after activin stimulation. In mice, AZD0530 blocked ectopic bone formation preserving limb movement.
Hypothesis: AZD0530 will reduce ectopic bone formation and progressive disability in people with FOP.
AIM: to provide proof of concept that AZD0530 is an effective drug in the treatment of patients with FOP.
Methods: Based on the rarity of the disease and expected drug efficacy (50% reduction in new bone), a phase 2A proof of concept study including a 6 month randomized placebo controlled study and 12 month open label extension study using historical data, is proposed including 16 adults with active FOP disease. The study will be performed in three European FOP expert Centers (Amsterdam The Netherlands – Lead, London UK, and Garmen Partenkirchen Germany). The study will be performed in collaboration with the expert preclinical teams at the Universities of Oxford and Harvard. FOP expert and patient engagement as well as safety will be ensured by establishing advisory, DSM and stakeholder boards. Early involvement of the regulatory agencies are planned.
Expectations: we will develop a roadmap for further studies and regulation of this new treatment option in FOP based on the results.
Ámbito científico
Palabras clave
Programa(s)
Tema(s)
Convocatoria de propuestas
H2020-JTI-IMI2-2017-13-two-stage
Consulte otros proyectos de esta convocatoriaRégimen de financiación
RIA - Research and Innovation actionCoordinador
1081 HV Amsterdam
Países Bajos