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An Efficacy and Safety Study of Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva. (MOVE)

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: NCT03312634
Recruitment Status : Active, not recruiting
First Posted : October 18, 2017
Last Update Posted : November 29, 2022
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) 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.

Condition or disease Intervention/treatment Phase
Fibrodysplasia Ossificans Progressiva Drug: Palovarotene Phase 3

Detailed Description:

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 that will be conducted in three parts: Part A, the main part of the study; Part B, the 24-month extension. 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).

And Part C, the up-to-2-year post last dose of study treatment follow-up for skeletally immature subjects. No new subjects will be enrolled into Part C. Subjects who were enrolled in Parts A or B who have discontinued the study and were skeletally immature will be invited back to participate in the off-treatment Part C safety follow-up.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 107 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: A multicenter, open-label study. NHS data (study PVO-1A-001) will be used as an external control in the analysis.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Efficacy and Safety Study of Oral Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)
Actual Study Start Date : November 30, 2017
Actual Primary Completion Date : January 24, 2020
Estimated Study Completion Date : November 2022

Arm Intervention/treatment
Experimental: Palovarotene Chronic/Flare-Up Regimen
Subjects will receive 5 mg palovarotene once daily for up to 24 months; and 20 mg palovarotene once daily for 28 days, followed by 10 mg for 56 days for flareups. (Dosing will be adjusted for weight in skeletally immature subjects.)
Drug: Palovarotene
Palovarotene will be taken orally once daily at approximately the same time each day following a meal.

Primary Outcome Measures :
  1. Change in New HO Volume [ Time Frame: Screening, every 6 months to 2 years ]
    Annualized change in new HO volume as assessed by low-dose, WBCT (excluding head) compared to untreated subjects from the NHS.

Secondary Outcome Measures :
  1. Subjects with New HO [ Time Frame: Screening, every 6 months for 2 years, then annually up to 4 years ]
    The proportion of subjects with any new HO.

  2. Number of Body Regions with HO [ Time Frame: Screening, every 6 months for 2 years, then annually up to 4 years ]
    Change from baseline in the number of body regions with new HO.

  3. Subjects with Flare-Ups [ Time Frame: Up to 4 years ]
    The proportion of subjects reporting flare-ups.

  4. Rate of Flare-Ups [ Time Frame: Up to 4 years ]
    The rate of flare-ups per subject-month exposure.

  5. Incidence of Adverse Events [ Time Frame: Up to 4 years ]
    Monitor adverse events.

  6. Palovarotene Area Under the Curve (AUC) [ Time Frame: Predose, and 3, 6, 10, and 24 hours postdose ]
    Determination of AUC at steady-state assessed during treatment with 5, 10, and 20 mg palovarotene.

Other Outcome Measures:
  1. Range of Motion [ Time Frame: Screening, every 6 months up to 4 years ]
    Change from baseline in range of motion as assessed by the Cumulative Analogue Joint Involvement Scale for FOP (CAJIS).

  2. FOP-Physical Function Questionnaire [ Time Frame: Screening, every 6 months up to 4 years ]
    Change from baseline in physical function using age-appropriate forms of the FOP-Physical Function Questionnaire (PFQ).

  3. PROMIS Global Health Scale [ Time Frame: Screening, every 6 months up to 4 years ]
    Change from baseline in physical/mental function using age-appropriate forms of the PROMIS Global Health Scale.

Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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): NCT03312634

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United States, California
University of California San Francisco, Division of Endocrinology and Metabolism
San Francisco, California, United States, 94143
United States, Minnesota
Mayo Clinic - PIN
Rochester, Minnesota, United States, 55905
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
University of Pennsylvania, Internal Medicine
Philadelphia, Pennsylvania, United States, 19104
Hospital Italiano de Buenos Aires, Tte General Juan Domingo Peron 4190
Buenos Aires, Argentina, C1199ACH
Australia, New South Wales
Royal North Shore Hospital
Saint Leonards, New South Wales, Australia, 2065
Australia, Queensland
Queensland University of Technology
Woolloongabba, Queensland, Australia, 4102
Hospital Israelita Albert Einstein
Sao Paulo, SP, Brazil, 05652-900
Canada, Ontario
Hospital for Sick Children, 555 University Avenue
Toronto, Ontario, Canada, M5G 1X8
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Groupe Hospitalier Necker Enfants Malades
Paris, France, 75015
Istituto Giannina Gaslini
Genoa, Liguria, Italy, 16147
The University of Tokyo Hospital
Tokyo, Bunkyo-ku, Japan, 113-8655
Hospital Universitari i Politècnic La Fe, Unidad de Reumatología Pediatrica
Valencia, Avinguda De Fernando Abril Martorell, Nº 106, Spain, 46026
Norrlands Universitetssjukhus
Umeå, Sweden, SE-90185
United Kingdom
Royal National Orthopaedic Hospital, Brockely Hill
Stanmore, United Kingdom, HA7 4LP
Sponsors and Collaborators
Clementia Pharmaceuticals Inc.
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Study Director: Ipsen Medical Director Ipsen
Additional Information:
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Responsible Party: Clementia Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT03312634    
Other Study ID Numbers: PVO-1A-301
2017-002541-29 ( EudraCT Number )
First Posted: October 18, 2017    Key Record Dates
Last Update Posted: November 29, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ipsen ( Clementia Pharmaceuticals Inc. ):
Myositis Ossificans Progressiva
FOP variants
Interventional study
Clinical trial phase 3
Efficacy and safety
Heterotopic ossification
Retinoic acid receptor agonist
Retinoic acid receptor gamma agonist
Munchmeyer's Disease
Additional relevant MeSH terms:
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Myositis Ossificans
Muscular Diseases
Musculoskeletal Diseases