Clinical Trial Finder

Key

Inclusion Criteria:

• - Written, signed, and dated informed subject/parent consent; and for subjects who are minors, age-appropriate assent (performed according to local regulations).

• - Males or females at least 4 years of age.

• - 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.

• - No flare-up symptoms within the past 4 weeks, including at the time of enrollment.

• - Abstinent or using two highly effective forms of birth control.

• - Accessible for treatment and follow-up; able to undergo all study procedures including low-dose WBCT (excluding head) without sedation.

Key

Exclusion Criteria:

• - Weight <10 kg.

• - Concomitant medications that are strong inhibitors or inducers of cytochrome P450 (CYP450) 3A4 activity; or kinase inhibitors such as imatinib.

• - Amylase or lipase >2x above the upper limit of normal (ULN) or with a history of chronic pancreatitis.

• - Elevated aspartate aminotransferase or alanine aminotransferase >2.5x ULN.

• - Fasting triglycerides >400 mg/dL with or without therapy.

• - Female subjects who are breastfeeding.

• - Subjects with uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, or other significant disease.

• - Simultaneous participation in another clinical research study (other than palovarotene studies) within 4 weeks prior to Screening; or within five half-lives of the investigational agent, whichever is longer.

• - Any reason that, in the opinion of the Investigator, would lead to the inability of the subject and/or family to comply with the protocol.

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. Eligible subjects will receive a chronic/flare-up dosing regimen of palovarotene for 24 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).