Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial.

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 .

Author Correction: The evolutionary history of lethal metastatic prostate cancer.

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Augmented exercise in hospital improves physical performance and reduces negative post hospitalization events: a randomized controlled trial.

BACKGROUND: To measure the effects of an augmented prescribed exercise programme versus usual care, on physical performance, quality of life and healthcare utilisation for frail older medical patients in the acute setting. METHODS: This was a parallel single-blinded randomised controlled trial. Within 2 days of admission, older medical inpatients with an anticipated length of stay ≥3 days, needing assistance/aid to walk, were blindly randomly allocated to the intervention or control group. Until discharge, both groups received twice daily, Monday-to-Friday half-hour assisted exercises, assisted by a staff physiotherapist. The intervention group completed tailored strengthening and balance exercises; the control group performed stretching and relaxation exercises. Length of stay was the primary outcome measure. Blindly assessed secondary measures included readmissions within 3 months, and physical performance (Short Physical Performance Battery) and quality of life (EuroQOL-5D-5 L) at discharge and at 3 months. Time-to-event analysis was used to measure differences in length of stay, and regression models were used to measure differences in physical performance, quality of life, adverse events (falls, deaths) and negative events (prolonged hospitalisation, institutionalisation). RESULTS: Of the 199 patients allocated, 190 patients' (aged 80 ± 7.5 years) data were analysed. Groups were comparable at baseline. In intention-to-treat analysis, length of stay did not differ between groups (HR 1.09 (95% CI, 0.77-1.56) p = 0.6). Physical performance was better in the intervention group at discharge (difference 0.88 (95% CI, 0.20-1.57) p = 0.01), but lost at follow-up (difference 0.45 (95% CI, - 0.43 - 1.33) p = 0.3). An improvement in quality of life was detected at follow-up in the intervention group (difference 0.28 (95% CI, 0.9-0.47) p = 0.004). Overall, fewer negative events occurred in the intervention group (OR 0.46 (95% CI 0.23-0.92) p = 0.03). CONCLUSION: Improvements in physical performance, quality of life and fewer negative events suggest that this intervention is of value to frail medical inpatients. Its effect on length of stay remains unclear. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02463864, registered prospectively 26.05.2015.