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.
Name: Palovarotene
Description: Palovarotene will be taken orally once daily at approximately the same time each day following a meal.Type: DrugPalovarotene Chronic/Flare-Up Regimen
Description: Annualized change in new HO volume as assessed by low-dose, WBCT (excluding head) compared to untreated subjects from the NHS.
Measure: Change in New HO Volume Time: Screening, every 6 months up to 2 yearsDescription: The proportion of subjects with any new HO.
Measure: Subjects with New HO Time: Screening, every 6 months up to 2 yearsDescription: Change from baseline in the number of body regions with new HO.
Measure: Number of Body Regions with HO Time: Screening, every 6 months up to 2 yearsDescription: The proportion of subjects reporting flare-ups.
Measure: Subjects with Flare-Ups Time: Up to 2 yearsDescription: The rate of flare-ups per subject-month exposure.
Measure: Rate of Flare-Ups Time: Up to 2 yearsDescription: Monitor adverse events.
Measure: Incidence of Adverse Events Time: Up to 2 yearsDescription: Determination of AUC at steady-state assessed during treatment with 5, 10, and 20 mg palovarotene.
Measure: Palovarotene Area Under the Curve (AUC) Time: Predose, and 3, 6, 10, and 24 hours postdoseDescription: Change from baseline in range of motion as assessed by the Cumulative Analogue Joint Involvement Scale for FOP (CAJIS).
Measure: Range of Motion Time: Screening, every 6 months up to 2 yearsDescription: Change from baseline in physical function using age-appropriate forms of the FOP-Physical Function Questionnaire (PFQ).
Measure: FOP-Physical Function Questionnaire Time: Screening, every 6 months up to 2 yearsDescription: Change from baseline in physical/mental function using age-appropriate forms of the PROMIS Global Health Scale.
Measure: PROMIS Global Health Scale Time: Screening, every 6 months up to 2 yearsSingle Group Assignment
There is one SNP
- Previous participation in Clementia's natural history study (NCT02322255); clinically diagnosed with FOP, with the R206H ACVR1 mutation or other FOP variants reported to be associated with progressive HO (who have not participated in any Clementia-sponsored study); participants in Clementia's Phase 2 studies (NCT02279095 and NCT02979769) who cannot currently receive the chronic/flare-up regimen due to country of residence or those traveling long distances to participate in the Phase 2 studies. --- R206H ---