Reduction of New Heterotopic Ossification (HO) in the Open ‐Label, Phase 3 MOVE Trial of Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP)
AbstractFibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely disabling genetic disorder of progressive heterotopic ossification (HO). The single-arm, open-label, phase 3 MOVE trial (NCT03312634) assessed efficacy and safety of palovarotene, a selective retinoic acid receptor gamma agonist, in patients with FOP. Findings were compared with FOP natural history study (NHS; NCT02322255) participants untreated beyond standard of care.Patients aged ≥4 years received palovarotene once-daily (chronic: 5 mg; flare-up: 20 mg for 4 weeks then 10 mg for ≥8 weeks; weight-adjusted if skeletally immature). The primary endpoint was annualized change in new HO volume versus NHS participants (by low-dose whole-body computed tomography [WBCT]), a nalyzed using a Bayesian compound Poisson model (BcPM) with square-root transformation. Twelve-month interim analyses met futility criteria; dosing was paused. An independent Data Monitoring Committee recommended trial continuation. Post hoc 18-month interim analyses utilized BcPM with square-root t ransformation and HO data collapsed to equalize MOVE and NHS visit schedules, BcPM without transformation, and weighted linear mixed-effects (wLME) models, alongside pre-specified analysis. Safety was assessed throughout.Eighteen-month interim analyses included 97 MOVE and 101 NHS individuals with post-Baseline WBCT. BcPM analyses without transformation showed 99.4% probability of any reduction in new HO with palovarotene versus ...
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Robert J. Pignolo,
Edward C. Hsiao,
Mona Al Mukaddam,
Genevi ève Baujat,
Staffan K. Berglund,
Matthew A. Brown,
Angela M. Cheung,
Carmen De Cunto,
Patricia Delai,
Nobuhiko Haga,
Peter Kannu,
Richard Keen,
Kim‐Hanh Le Quan Sang,
Edna E. Man Tags: Clinical Trial Source Type: research
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