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 (RARĪ³) 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 monthsAllocation: Non-Randomized
Parallel Assignment
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 ---