Ensayos clínicos

Inclusion Criteria:

- Participant has completed the EOS or End of Treatment Visit of Study PVO-1A-301 or
PVO-1A-202 (PVO-1A-202 Parts C and D correspond to Study PVO-1A-204 in France) and did
not previously withdraw consent from any of the parent studies to be eligible for
Study CLIN-60120-452.

- Participant must be ≥ 14 years of age (aligned with the age of treated participants in
the ongoing parent studies PVO-1A-301 and PVO-1A-202/PVO-1A-204) and qualify as 100%
skeletally mature (if < 18 years, based on assessments carried out at parent EOS Visit;
if ≥ 18 years, automatically considered 100% skeletally mature) or have reached final
adult height based on investigator's assessment, at the time the Study CLIN- 60120-452
informed consent is signed.

Exclusion Criteria:

- History of allergy or hypersensitivity to retinoids, gelatin, lactose (note that
lactose intolerance is not exclusionary) or palovarotene, or unresponsiveness to prior
treatment with palovarotene.

- Uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine,
metabolic, ophthalmologic, immunologic, psychiatric, or other significant disease.

- Intercurrent known or suspected non-healed fracture at any location;

- Any other medical condition/clinically significant abnormalities that would expose the
participant to undue risk or interfere with study assessments.

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

- Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN.

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

- Suicidal ideation (type 4 or 5) or any suicidal behaviour at the Inclusion Visit as
defined by the Columbia-Suicide Severity Rating Scale (C-SSRS).

- Current use of 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 within 4 weeks of the
Inclusion Visit.

- Concurrent treatment with tetracycline or any tetracycline derivatives due to the
potential increased risk of pseudotumor cerebri.

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

- Palovarotene is commercially available in the country where the study is being
conducted.

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

Eligibility last updated 7/1/22. Questions regarding updates should be directed to the study team contact.