for people ages 6-65 (full criteria)
at San Francisco, California and other locations
study started
estimated completion
Principal Investigator
by Edward Hsiao
Photo of Edward Hsiao
Edward Hsiao



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. In this study, the ability of palovarotene to prevent HO formation will be evaluated.

Official Title

A Phase 2, Open-Label Extension, Efficacy and Safety Study of a RARγ Specific Agonist (Palovarotene) in the Treatment of Preosseous Flare-ups in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)


The main objective of this Phase 2, multicenter, open-label study is to evaluate the safety and efficacy of different palovarotene dosing regimens in subjects with FOP. In Part A, all subjects who completed Study PVO-1A-201 and enrolled into the current study received daily treatment with open-label palovarotene for an eligible flare-up at a dose of 10 mg for 14 days, followed by 5 mg for 28 days (or the weight-based equivalent). Part A is completed. In Part B, subjects with at least 90% skeletal maturity were treated with 5 mg palovarotene on a daily basis (ie, chronically). In the event of an eligible flare-up, all subjects received 20 mg palovarotene daily for 28 days, followed by 10 mg for 56 days (dosing was weight-based in subjects who were skeletally immature). Dosing could be extended if the flare-up was not resolved by Flare-up Day 84 and continued until the flare-up resolved. Dose reduction, as directed by the Investigator, occurred in the event of intolerable side effects. The duration of Part B is up to 24 months. In Part C, the dosing regimens implemented in Part B will continue except that subjects with less than 90% skeletal maturity will now receive chronic daily administration of palovarotene (5 mg, or the weight-based equivalent). The assessment of HO will occur every 12 months using low-dose, whole body computed tomography (WBCT), excluding head; other efficacy and safety outcomes will be evaluated remotely every 3 months, or monthly during flare-up based treatment. The duration of Part C is 36 months.


Fibrodysplasia Ossificans Progressiva Open-label extension study Clinical trial Phase 2 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 Myositis Ossificans Palovarotene dose level 1 Palovarotene dose level 2 Palovarotene dose level 3 Palovarotene dose level 4


You can join if…

Open to people ages 6-65

  • Completion of Study PVO-1A-202/Part B.
  • Written, signed, and dated informed consent and, for subjects who are minors, age-appropriate subject assent (performed according to local regulations).
  • Accessible for treatment with palovarotene and follow-up (able and willing to travel to a site for the initial and all follow-up clinic visits).
  • Able to undergo low-dose, WBCT scan, excluding head.
  • Females of child-bearing potential 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 from heterosexual sex during treatment and for 1 month after treatment or, if sexually active, to use two effective methods of birth control during and for 1 month after treatment. Additionally, sexually active FOCBP subjects must already be using two 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 effective methods of birth control will be clearly defined in the informed consent and the subject or legally authorized representatives.

You CAN'T join if...

  • 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.
  • Amylase or lipase >2x above the upper limit of normal or with a history of pancreatitis.
  • Elevated aspartate aminotransferase or alanine aminotransferase >2.5x the upper limit of normal.
  • Fasting triglycerides >400 mg/dL with or without therapy.
  • If currently using vitamin A or beta carotene, multivitamins containing vitamin A or beta carotene, herbal preparations containing vitamin A or beta carotene, or fish oil, and unable or unwilling to discontinue use of these products during palovarotene treatment.
  • Subjects experiencing suicidal ideation (type 4 or 5) or any suicidal behavior within the past month as defined by the Columbia Suicide Severity Rating Scale (C-SSRS).


  • University of California San Francisco, Division of Endocrinology and Metabolism
    San Francisco California 94143 United States
  • Mayo Clinic, Department of Medicine
    Rochester Minnesota 55905 United States

Lead Scientist at UCSF

  • Edward Hsiao
    Residency: Johns Hopkins Hospital, Baltimore, MD, Internal Medicine, 2001-2004 Fellowship: UCSF, Division of Diabetes, Endocrinology and Metabolism, 2004-2007 Board Certifications: Internal Medicine, 2004; Endocrinology and Metabolism, 2006 My research is driven by a desire to understand how major hormonal and regulatory pathways determine the specification, differentiation, a…


in progress, not accepting new patients
Start Date
Completion Date
Clementia Pharmaceuticals Inc.
more information about this study: A Phase 2, Open-Label Extension, Efficacy and Safety Study of a RARγ-Specific Agonist (Palovarotene) in the Treatment of Preosseous Flare-ups in Subjects with Fibrodysplasia Ossificans Progressiva (FOP)
Phase 2
Study Type
Last Updated