Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by painful, recurrent episodes of soft tissue swelling (flare-ups) that result in abnormal bone formation (heterotopic ossification or HO) in muscles, tendons, and ligaments. Flare-ups begin early in life and may occur spontaneously or after soft tissue trauma, vaccinations, or influenza infections. Recurrent flare-ups progressively restrict movement by locking joints leading to cumulative loss of function and disability. Mouse models of FOP have demonstrated the ability of retinoic acid receptor gamma (RARγ) agonists such as palovarotene (PVO) to prevent HO following injury. Study PVO-1A-201 as well as up to two new adult subjects were followed for up to 24 months. Subjects who participated under Amendment 1 will be followed for up to an additional 36 months. No new subjects will be enrolled.
Name: Palovarotene dose level 1
Name: Palovarotene dose level 2
Description: The annualized change from the original protocol, and Amendments 1 and 3, will be compared to data collected from the Natural History Study (NHS).Measure: Annualized change in new HO volume as assessed by low-dose WBCT scan, excluding head Time: Annually until the end of study (36 months)
Description: Cumulative Analogue Joint Involvement Scale (CAJIS) for FOP assesses functional disability by categorizing range of motion across 12 joints and three body regions with each joint/region assessed as: 0=uninvolved; 1=affected; 2=functionally ankylosed.Measure: Change from baseline in range of motion (ROM) as assessed by CAJIS Time: baseline, 6, 12, 18, 24, 30 and 36 months
There is one SNP
Inclusion Criteria: - Completion of Study PVO-1A-201; or new Adult Cohort subjects with confirmed R206H mutation who (1) have had at least two symptomatic flare-ups in the past 2 years, but no flare-up symptoms within the past 4 weeks; (2) have a Cumulative Analogue Joint Involvement for FOP (CAJIS) score of 6-16 (inclusive); and (3) are able to receive 5 mg palovarotene daily. --- R206H ---