An Efficacy and Safety Study of Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva.
Condition: Fibrodysplasia Ossificans Progressiva
MeSH terms: Myositis Ossificans
Intervention: Palovarotene
Intervention description: Palovarotene was taken orally once daily at approximately the same time each day following a meal.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: A multicenter, open-label study. NHS data (study PVO-1A-001) will be used as an external control in the analysis.
Masking: None (Open Label)
Enrollment: 107.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: Interventional study; Clinical trial phase 3; Efficacy and safety; Heterotopic ossification; Flare-up; Palovarotene; Retinoic acid receptor agonist; Retinoic acid receptor gamma agonist; Clementia; Myositis Ossificans Progressiva; Munchmeyer's Disease; FOP; FOP variants

Summary:

      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.
    

Eligibility criteria:

        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.

          -  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.