Objectives:
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by heterotopic ossification (HO) and progressive disability. Until the recent approval of palovarotene in Canada, no licensed disease-modifying treatments for FOP existed, but interim phase III trial (NCT03312634) results suggest marked efficacy for palovarotene (PVO).1 Here, we describe methodology of the PIVOINE trial (NCT05027802) designed to allow treatment continuity and further evaluation of PVO safety and efficacy.
Methods:
Patients will receive 5 mg PVO once 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, in line with parent studies. Enrollment criteria: completion of a parent study (end of study/treatment visit of NCT03312634 or NCT02279095/NCT02979769), ≥14 years old, full skeletal maturity if aged <18 or deemed to be final height. PIVOINE aims to enroll 87 patients; recruitment began in March. Outcomes are presented in the Table.
Summary:
Results from PIVOINE, estimated to end in November 2024, will allow further evaluation of PVO in FOP.
Funding: Sponsored by Ipsen.
Table: Trial outcomes
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Primary |
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Incidence of treatment-emergent adverse eventsa |
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Secondaryb |
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Cumulative Analogue Joint Involvement Scale total scorec |
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Use of aids, assistive devices and adaptationsc |
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FOP-Physical Function Questionnaire % of worst score (total score; upper extremities/mobility sub-scores)c |
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Frequency/type of healthcare services utilization |
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Observed/percentage predicted (PP):c Forced vital capacity (FVC) Forced expiratory volume in 1 second (FEV1) Diffusion capacity of the lung for carbon monoxide Absolute/PP:c FEV1/FVC ratio |
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Patient Reported Outcomes Measurement Information System physical and mental function scoresc |
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Number of reported flare-ups, outcomes and durationc |
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% of patients with new bone growthcd |
aCollected continuously over trial; bCollected every 6 months over trial; cRaw values and change from inclusion visit; dNot based on scans.
Disclosures: AA, PM, KC: Employees of Ipsen.