Descrizione del progetto
Una nuova sperimentazione per il trattamento di disturbi rari
La fibrodisplasia ossificante progressiva (FOP) è una rara malattia ereditaria del tessuto connettivo. La FOP, causata da una mutazione del gene ACVR1 e caratterizzata dalla progressiva ossificazione eterotopica del tessuto fibroso, provoca la paralisi. Le persone affette vivono mediamente fino ai 40 anni di età. In assenza di trattamenti attualmente approvati per il trattamento della FOP, il progetto STOPFOP esaminerà la possibilità di utilizzare il farmaco sperimentale AZD0530, anche noto con il nome commerciale di saracatinib. Lo studio sarà condotto in tre centri di competenza per la FOP in Germania, nei Paesi Bassi e nel Regno Unito. L’obiettivo generale del progetto è fornire la prova di concetto che AZD0530 è un farmaco efficace per il trattamento della FOP.
Obiettivo
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.
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RIA - Research and Innovation actionCoordinatore
1081 HV Amsterdam
Paesi Bassi