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An Open-Label Extension Study of Palovarotene to Prevent Heterotopic Ossification in People With Fibrodysplasia Ossificans Progressiva (FOP) in France

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02979769
Recruitment Status : Completed
First Posted : December 2, 2016
Last Update Posted : July 29, 2022
Sponsor:
Information provided by (Responsible Party):
Ipsen ( Clementia Pharmaceuticals Inc. )

Brief Summary:

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by heterotopic ossification (HO), i.e., abnormal bone formation, often associated with painful, recurrent episodes of soft tissue swelling (flare-ups). Lesions begin in early childhood and lead to progressive ankyloses of major joints with resultant loss of movement.

In this study, the ability of different palovarotene dosing regimens to prevent the formation of new HO will be evaluated in adult and pediatric participants with FOP in France.


Condition or disease Intervention/treatment Phase
Fibrodysplasia Ossificans Progressiva Drug: Palovarotene Phase 2

Detailed Description:

The main objective of this Phase 2, open-label study is to evaluate the safety and efficacy of different palovarotene dosing regimens in participants with FOP in France. Efficacy will be assessed based on the ability of palovarotene to prevent the formation of new heterotopic ossification (HO) as assessed by low-dose whole body computed tomography (WBCT) scan, excluding head.

Participants who successfully completed study PVO-1A-201 as well as up to two new adult participants were followed for up to 24 months. Participants under Amendment 1 will be followed for up to an additional 48 months. No new participants will be enrolled.

The Adult Cohort will include all participants with at least 90% skeletal maturity, regardless of age. The Pediatric Cohort will include all participants with less than 90% skeletal maturity. Any Pediatric Cohort participants who achieves ≥90% skeletal maturity during the study can be considered for enrollment into the Adult Cohort at the discretion of then Investigator.

Participants that were skeletally immature at their last assessment will be invited back to participate in a safety follow-up (Part D) that includes yearly visits for up to a 2-year follow-up period following last dose. No dosing will occur in Part D.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label Extension, Efficacy and Safety Study of a Retinoic Acid Receptor Gamma (RARγ)-Specific Agonist (Palovarotene) in the Treatment of Preosseous Flare-ups in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)
Actual Study Start Date : November 28, 2016
Actual Primary Completion Date : June 28, 2022
Actual Study Completion Date : June 28, 2022


Arm Intervention/treatment
Experimental: Palovarotene

All participants will receive non-flare-up based treatment of 5 mg palovarotene once daily for 24 months.

Participants who continued non-flare-up based treatment under Amendment 1 will receive non-flare-up based treatment for up to an additional 48 months (therefore 72 months over the entire study).

Participants who start non-flare-up based treatment under Amendment 1 will receive non-flare-up based treatment for up to 48 months.

Participants that are skeletally immature will receive weight-adjusted doses.

In the event of an eligible flare-up all participants will receive 20 mg palovarotene for 28 days, followed by 10 mg palovarotene for 56 days. Participants under the age of 18 years will receive weight-adjusted doses.

Drug: Palovarotene
Palovarotene will be taken orally once daily at approximately the same time each day.




Primary Outcome Measures :
  1. Annualized change in new HO volume [ Time Frame: Every 12 months until the end of the study (up to 72 months) ]
    Assessed by low-dose whole body computed tomography (WBCT) (excluding head)


Secondary Outcome Measures :
  1. Percent of participants with new HO [ Time Frame: Every 12 months for up to 72 months ]
  2. Change from baseline in range of motion (ROM) [ Time Frame: Every 6 months for up to 72 months ]
    Assessed by Cumulative Analogue Joint Involvement Scale (CAJIS)

  3. Change from baseline in physical function [ Time Frame: Every 6 months for up to 72 months ]
    Assessed by age-appropriate forms of the FOP-Physical Function Questionnaire (FOP-PFQ)

  4. Change from baseline in physical and mental function for participants ≥15 years old and mental function for participants <15 years old [ Time Frame: Every 6 months for up to 72 months ]
    Assessed by age-appropriate forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale



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Ages Eligible for Study:   6 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Prior participation in Amendment 1 of the current study (PVO-1A-204).
  • Written, signed, and dated informed consent and, for participants who are minors, age-appropriate participant 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 (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 participants 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 participants 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 participant or legally authorized representatives.

Exclusion Criteria:

  • 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.
  • 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.
  • Participants 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02979769


Locations
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France
Hôpital Necker-Enfants Malades, Department of Genetics
Paris, France
Sponsors and Collaborators
Clementia Pharmaceuticals Inc.
Investigators
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Study Director: Ipsen Medical Director Ipsen
Additional Information:
Publications:
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Responsible Party: Clementia Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02979769    
Other Study ID Numbers: PVO-1A-204
2016-002526-36 ( EudraCT Number )
First Posted: December 2, 2016    Key Record Dates
Last Update Posted: July 29, 2022
Last Verified: July 2022
Keywords provided by Ipsen ( Clementia Pharmaceuticals Inc. ):
Open-label extension study
Clinical trial Phase 2
Efficacy and safety
Heterotopic ossification
Flare-up
Palovarotene
Retinoic acide receptor agonist
Retinoic acide receptor gamma agonist
Clementia
Myositis Ossificans
Munchmeyer's Disease
FOP
Ipsen
Additional relevant MeSH terms:
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Myositis Ossificans
Myositis
Muscular Diseases
Musculoskeletal Diseases