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

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. Identifier: NCT03312634
Recruitment Status : Active, not recruiting
First Posted : October 18, 2017
Last Update Posted : January 30, 2019
Information provided by (Responsible Party):
Clementia Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE October 9, 2017
First Posted Date  ICMJE October 18, 2017
Last Update Posted Date January 30, 2019
Actual Study Start Date  ICMJE November 28, 2017
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 12, 2017)
Change in New HO Volume [ Time Frame: Screening, every 6 months up to 2 years ]
Annualized change in new HO volume as assessed by low-dose, WBCT (excluding head) compared to untreated subjects from the NHS.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03312634 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2017)
  • Subjects with New HO [ Time Frame: Screening, every 6 months up to 2 years ]
    The proportion of subjects with any new HO.
  • Number of Body Regions with HO [ Time Frame: Screening, every 6 months up to 2 years ]
    Change from baseline in the number of body regions with new HO.
  • Subjects with Flare-Ups [ Time Frame: Up to 2 years ]
    The proportion of subjects reporting flare-ups.
  • Rate of Flare-Ups [ Time Frame: Up to 2 years ]
    The rate of flare-ups per subject-month exposure.
  • Incidence of Adverse Events [ Time Frame: Up to 2 years ]
    Monitor adverse events.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 12, 2017)
  • Range of Motion [ Time Frame: Screening, every 6 months up to 2 years ]
    Change from baseline in range of motion as assessed by the Cumulative Analogue Joint Involvement Scale for FOP (CAJIS).
  • FOP-Physical Function Questionnaire [ Time Frame: Screening, every 6 months up to 2 years ]
    Change from baseline in physical function using age-appropriate forms of the FOP-Physical Function Questionnaire (PFQ).
  • PROMIS Global Health Scale [ Time Frame: Screening, every 6 months up to 2 years ]
    Change from baseline in physical/mental function using age-appropriate forms of the PROMIS Global Health Scale.
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE An Efficacy and Safety Study of Palovarotene for the Treatment of FOP
Official Title  ICMJE MOVE TRIAL: A Phase 3, Efficacy and Safety Study of Oral Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)
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.
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. Eligible subjects will receive a chronic/flare-up dosing regimen of palovarotene for 24 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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
A multicenter, open-label study. Untreated subjects from the FOP NHS will serve as the control arm.
Masking: None (Open Label)
Masking Description:
None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fibrodysplasia Ossificans Progressiva
Intervention  ICMJE Drug: Palovarotene
Palovarotene will be taken orally once daily at approximately the same time each day following a meal.
Study Arms  ICMJE 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.)
Intervention: Drug: Palovarotene
Publications * Shimono K, Tung WE, Macolino C, Chi AH, Didizian JH, Mundy C, Chandraratna RA, Mishina Y, Enomoto-Iwamoto M, Pacifici M, Iwamoto M. Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-γ agonists. Nat Med. 2011 Apr;17(4):454-60. doi: 10.1038/nm.2334. Epub 2011 Apr 3. Erratum in: Nat Med. 2012 Oct;18(10):1592.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: July 7, 2018)
Original Estimated Enrollment  ICMJE
 (submitted: October 12, 2017)
Estimated Study Completion Date  ICMJE November 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Brazil,   Canada,   France,   Italy,   Japan,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03312634
Other Study ID Numbers  ICMJE PVO-1A-301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Clementia Pharmaceuticals Inc.
Study Sponsor  ICMJE Clementia Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Clementia Pharmaceuticals Inc.
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP