ODP108 Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva: Methodology of the Phase III Open-Label PIVOINE Rollover Trial

OBJECTIVES: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized byheterotopic ossification (HO) and progressive restriction of mobility. To date, no approved disease-modifying treatments for FOP exist, but interim phaseIII MOVE trial (NCT03312634) results suggest marked efficacy for palovarotene (PVO). 1 The PIVOINE rollover trial (NCT05027802) has been designed to allow treatment continuity and further evaluation of PVO safety and efficacy; the methodology is given here. METHODS: Patients will receive 5 mg PVO daily, or the parent study completion dose, for a maximum of 3 years; during flare-ups, patients will receive 20 mg daily for 4 weeks, then 10 mg daily for 8 weeks. Enrollment criteria: completion of a parent study (end of study/treatment visit of NCT03312634 or NCT02279095/NCT02979769), ≥14 years of age, full skeletal maturity if aged <18 or deemed to be final adult height. PIVOINE aims to enroll 61 patients; recruitment has not begun. The primary outcome will be the incidence and description of all treatment-emergent adverse events, collected continuously over the study period. Secondary outcomes (collected every 6 months; reported as raw values and change from the inclusion visit for outcomes specified by *) include: range of motion* (using Cumulative Analogue Joint Involvement Scale total score), the use of aids, assistive devices and adaptations*, physical function* (using adult form of the FOP-Physical Function Questionnaire; total score and upper extremities and mobility sub-scores), the frequency of healthcare utilization, and physical and mental health* (using Patient Reported Outcomes Measurement Information System Global Health Scale). Lung function will be assessed via observed and percentage predicted (PP) forced vital capacity (FVC)*, forced expiratory volume in 1 second (FEV 1)*, diffusion capacity of the lung for carbon monoxide*, and the absolute and PP FEV 1 /FVC ratio*. The number of investigator-reported flare-ups*, including duration and outcomes, will be reported along with the percentage of patients with new bone growth. SUMMARY: Results from PIVOINE, estimated to end in November 2024, will allow further evaluation of PVO in FOP. REFERENCES: 1. Pignolo R et al. ASBMR 2020;35(Suppl 1): 16–17 Funding: Sponsored by Ipsen. Presentation: No date and time listed