This study is in progress, not accepting new patients

An Efficacy and Safety Study of Palovarotene for the Treatment of FOP

a study on Fibrodysplasia Ossificans Progressiva

Summary

Eligibility
for people ages 4 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion
Principal Investigator
Edward Hsiao
Photo of Edward Hsiao
Edward Hsiao

Description

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.

Official Title

A Phase 3, Efficacy and Safety Study of Oral Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)

Details

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 48 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).

Keywords

Fibrodysplasia Ossificans Progressiva 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 Myositis Ossificans

Eligibility

For people ages 4 years and up

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.

Locations

  • University of California San Francisco, Division of Endocrinology and Metabolism
    San Francisco California 94143 United States
  • Mayo Clinic - 200 1st Street Southwest
    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…

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Clementia Pharmaceuticals Inc.
Links
Website for the International FOP Association
ID
NCT03312634
Phase
Phase 3
Study Type
Interventional
Last Updated