Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by heterotopic ossification (HO) often associated with painful, recurrent episodes of soft tissue swelling (flare-ups) that lead to ankyloses of major joints with cumulative and irreversible loss of movement and disability.
A Phase 3, Efficacy and Safety Study of Oral Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)
One primary objective is to evaluate the efficacy of palovarotene in decreasing new HO in subjects with FOP as assessed by low-dose, whole body computed tomography (WBCT), excluding head, compared to untreated subjects from Clementia's FOP natural history study (Study PVO-1A-001, NHS). The other primary objective is to evaluate the safety of palovarotene in subjects with FOP. This is a Phase 3, multicenter, open-label study that will be conducted in three parts: Part A, the main part of the study; Part B, the 24-month extension. Eligible subjects will receive a chronic/flare-up dosing regimen of palovarotene for 48 months as follows: - Chronic treatment: orally administered 5 mg palovarotene once daily for 24 months. - Flare-up treatment: orally administered 20 mg palovarotene once daily for 4 weeks (28 days) followed by orally administered 10 mg palovarotene once daily for 8 weeks (56 days). Flare-up treatment may be extended until the Investigator determines that the flare-up has resolved. Note that all dosing will be weight-adjusted in skeletally immature subjects (those under the age of 18 years with less than 90% skeletal maturity on hand/ wrist x-rays performed at Screening). And Part C, the up-to-2-year post last dose of study treatment follow-up for skeletally immature subjects. No new subjects will be enrolled into Part C. Subjects who were enrolled in Parts A or B who have discontinued the study and were skeletally immature will be invited back to participate in the off-treatment Part C safety follow-up.