Project description DEENESFRITPL New trial to treat rare disorder First identified in the 18th century, fibrodysplasia ossificans progressiva (FOP) is a rare inherited connective tissue disorder. Caused by a mutation in the ACVR1 gene and characterised by the progressive heterotopic ossification of fibrous tissue, FOP results in paralysis. Sufferers have an average life expectancy of 40. While there is currently no approved treatment, the EU-funded STOPFOP project will study whether the investigative drug AZD0530, also known as saracatinib, could be used to treat FOP. The study will be performed in three FOP expert centres in Germany, the Netherlands and the United Kingdom. The project’s overall aim is to provide proof of concept that AZD0530 is an effective drug in the treatment of patients with FOP. Show the project objective Hide the project objective Objective 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. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutation Programme(s) H2020-EU.3.1. - SOCIETAL CHALLENGES - Health, demographic change and well-being Main Programme H2020-EU.3.1.7. - Innovative Medicines Initiative 2 (IMI2) Topic(s) IMI2-2017-13-15 - Pilot programme on a Clinical Compound Bank for Repurposing: Rare/orphan diseases Call for proposal H2020-JTI-IMI2-2017-13-two-stage See other projects for this call Funding Scheme RIA - Research and Innovation action Coordinator STICHTING VUMC Net EU contribution € 568 239,00 Address De boelelaan 1117 1081 HV Amsterdam Netherlands See on map Region West-Nederland Noord-Holland Groot-Amsterdam Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,75 Participants (5) Sort alphabetically Sort by Net EU contribution Expand all Collapse all THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD United Kingdom Net EU contribution € 1 875,00 Address Wellington square university offices OX1 2JD Oxford See on map Region South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 BRIGHAM INC United States Net EU contribution € 1 875,00 Address Francis street 75 02115 Boston ma See on map Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 THE ROYAL NATIONAL ORTHOPAEDIC HOSPITAL NATIONAL HEALTH SERVICE TRUST United Kingdom Net EU contribution € 189 418,00 Address Brockley hill HA7 4LP Stanmore See on map Region London Outer London — West and North West Harrow and Hillingdon Activity type Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,75 KLINIKUM GARMISCH-PARTENKIRCHEN GMBH Germany Net EU contribution € 238 303,00 Address Auenstrasse 6 82467 Garmisch partenkirchen See on map Region Bayern Oberbayern Garmisch-Partenkirchen Activity type Other Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,75 ASTRAZENECA AB Sweden Net EU contribution € 0,00 Address Vastra maelarhamnen 151 85 Sodertaelje See on map Region Östra Sverige Stockholm Stockholms län Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 1 000 000,00
