ABSTRACT
Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths (5 of 44; 11.4%) occurred in the open-label period and, while considered unlikely to be related, causality cannot be ruled out. The primary efficacy end point in period 1 (total lesion activity by PET-CT) was not met (P = 0.0741). As the development of new HO lesions was suppressed in period 1, the primary efficacy end point in period 2 was prospectively changed to the number of new HO lesions versus period 1. No placebo patients crossing over to garetosmab developed new HO lesions (0% in period 2 versus 40.9% in period 1; P = 0.0027). Further investigation of garetosmab in FOP is ongoing. ClinicalTrials.gov identifier NCT03188666 .
Subject(s)
Myositis Ossificans , Ossification, Heterotopic , Adult , Humans , Myositis Ossificans/drug therapy , Myositis Ossificans/pathology , Positron Emission Tomography Computed Tomography , Ossification, Heterotopic/pathologySubject(s)
Biodiversity , Conservation of Natural Resources/legislation & jurisprudence , Environmental Policy/legislation & jurisprudence , Urban Renewal , Animals , Animals, Wild/virology , COVID-19/prevention & control , COVID-19/transmission , China , Cities/economics , Cities/statistics & numerical data , Food Supply/legislation & jurisprudence , Surveys and Questionnaires , Urban Renewal/economics , Viral Zoonoses/epidemiology , Viral Zoonoses/prevention & controlABSTRACT
An amendment to this paper has been published and can be accessed via a link at the top of the paper.