ECE2020 Oral Communications Bone and Calcium (7 abstracts)
STOPFOP: A european phase II clinical trial using saracatinib to prevent FOP
Bernard Smilde 1 , Richard Keen 2 , Clemens Stockklausner 3 , Dong Liu 4 , Alex Bullock 5 , Annette Von Delft 6 , Natasja Van Schoor 7 , Paul Yu 8 & Elisabeth Eekhoff 9
1Amsterdam UMC, location VUmc, Internal Medicine Section Endocrinology, Amsterdam, Netherlands; 2Royal National Orthopaedic Hospital, Department of Rheumatology, Middlesex and London, United Kingdom; 3Klinikum Garmisch-Partenkirchen GmbH Abteilung für Kinderklinik, Department of Paediatrics, Garmisch-Partenkirchen, Germany; 4Astrazeneca, Boston, United States; 5University of Oxford, Nuffield department of Medicine, Oxford, United Kingdom; 6University of Oxford, Nuffield department of Medicine, Oxford, United Kingdom; 7Amsterdam UMC, locatie VUmc, Epidemiology and biostatistics, Amsterdam, Netherlands; 8Brigham and Women’s Hospital - Department of Cardiovascular Medicine, Department of Medicine, Boston, United States; 9Amsterdam UMC, location VUmc, Internal Medicine section Endocrinology, Amsterdam, Netherlands
Background: Fibrodysplasia ossificans progressiva (FOP) is a rare, genetic and devastating disease characterized by progressive heterotopic ossifications (HO) in muscles, tendons, ligaments and fascia. The formation of HO leads to severe contractures and early death. There are no approved medications yet. The STOPFOP team identified AZD0530 (saracatinib) as a potent, low nanomolar inhibitor of the mutant ALK2 kinase which is the unique genetic driver of this rare bone disease. AZD0530 was proven to be effective in representative FOP mouse models. The European Union’s Innovative Medicines Initiative (IMI) has provided funding to investigate the repurposing of this drug, originally designed for ovarian cancer treatment, to treat patients with FOP.
Methods: This is a phase 2a study, designed as an European multicentre 6-month double blind randomized controlled trial (RCT) of AZD0530 vs placebo, followed by a 12 month trial comparing open-label extended AZD0530 treatment with historical control data. In total 20 FOP patients, aged 18 to 65 years, will be included with the classic FOP mutation (R206H). Endpoints are objective change in heterotopic bone volume measured by low-dose whole body computer tomography (CT) , [18F] NaF PET activity and patient reported outcome measures (PROMS).
Discussion: Drug repurposing – using existing clinical molecules for new disease indications - presents an ideal solution for limiting risks in early clinical studies where there is a supporting genetic rationale for the drug in question. This is especially useful in rare diseases, as the study population is limited. Using existing assets and investments, may also allow more affordable pricing once an indication is approved. AZD0530 would represent a rapidly translatable therapy for FOP, having the significant advantage of extensive safety data from over 28 registered clinical trials with AZD0530 involving over 600 patients. Trial registration EudraCT number 2019-003324-20
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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