Clinical Trials

Study Population (Adult and Pediatric Cohorts – Part B)

Inclusion Criteria:

• Completion of Study PVO-1A-201 (through Study Day 84) or Adult Cohort subjects not enrolled in Study PVO-1A-201.
• Have the confirmed R206H genetic mutation consistent with FOP.
• Have had at least two acute symptomatic flare-ups in the past 2 years but no flare-up symptoms within the past 4 weeks, including at the time of enrollment.
• Have a CAJIS score of 6 to 16, inclusive, and must be able to receive non-flare-up based dosing.
• For the Adult Cohort, subjects under the age of 18 must have knee and hand/wrist radiographs confirming ≥ 90% skeletal maturity.
• Written, signed, and dated subject/parent informed consent; and, for subjects who are minors, age-appropriate assent (this must be performed acording to local regulations).

Exclusion Criteria:

• Simultaneous participation in another clinical research study (except for Studies PVO-1A-201, PVO-1A-203, or PVO-1A-001) within 4 weeks prior to Part B Screening.
• 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.

Study Population for Non-Flare-up Based Treatment (Adult Cohort - Part B)

Inclusion Criteria:

• Females of child-bearing potential (FOCBP) must have a negative blood or urine pregnancy test (with sensitivity of at least 50 mIU/mL) prior to administration of palovarotene. Male and FOCBP subjects must agree to remain abstinent during treatment and for 1 month after treatment or, if sexually active, to use two highly effective methods of birth control during and for 1 month after treatment. Additionally, sexually active FOCBP subjects must already be using two highly effective methods of birth control 1 month before treatment is to start.  Specific risk of the use of retinoids during pregnancy, and the agreement to remain abstinent or use two highly effective methods of birth control will be clearly defined in the informed consent and the subject or legally authorized representatives (e.g., parents, caregivers, or legal guardians) must specifically sign this section.
• Subjects must be accessible for treatment with palovarotene and follow-up. Subjects living at distant locations from the investigational site must be able and willing to travel to a site for the initial and all on-site follow-up visits.

Exclusion Criteria:

• Weight < 20 kg.
• Intercurrent known or suspected non-healed fracture at any location.
• If currently using vitamin A or beta carotene, multivitamins containing vitamin A or beta carotene, or herbal preparations, fish oil, and unable or unwilling to discontinue use of these products during palovarotene treatment.
• Exposure to synthetic oral retinoids other than palovarotene in the past 30 days prior to Part B Screening (signature of the informed consent).
• Concurrent treatment with tetracycline or any tetracycline derivatives due to the potential increased risk of pseudotumor cerebri.
• History of allergy or hypersensitivity to retinoids or lactose.
• Concomitant medications that are inhibitors or inducers of cytochrome P450 (CYP450) 3A4 activity.
• Amylase or lipase > 2x above the upper limit of normal (ULN) or with a history of chronic pancreatitis.
• Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 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.
• Subjects experiencing suicidal ideation (type 4 or 5) or any suicidal behavior within the past month as defined by the C-SSRS.