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Trial record 9 of 29 for:    fop

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

This study is not yet open for participant recruitment.
Verified October 2017 by Clementia Pharmaceuticals Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03312634
First Posted: October 18, 2017
Last Update Posted: November 16, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Clementia Pharmaceuticals Inc.
October 9, 2017
October 18, 2017
November 16, 2017
November 2017
September 2020   (Final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT03312634 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
  • 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.
Same as current
 
An Efficacy and Safety Study of Palovarotene for the Treatment of FOP
MOVE TRIAL: A Phase 3, Efficacy and Safety Study of Oral Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)
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.

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).

Interventional
Phase 3
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
Fibrodysplasia Ossificans Progressiva
Drug: Palovarotene
Palovarotene will be taken orally once daily at approximately the same time each day following a meal.
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
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 ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
80
November 2020
September 2020   (Final data collection date for primary outcome measure)

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.
  • Clinically diagnosed with FOP, with the R206H ACVR1 mutation.
  • 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).

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 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.
Sexes Eligible for Study: All
4 Years and older   (Child, Adult, Senior)
No
Contact: Clinical Trials Information 1-800-750-8710 ClinicalTrials@clementiapharma.com
Contact: Clinical Trials Information
Not Provided
 
 
NCT03312634
PVO-1A-301
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Undecided
Clementia Pharmaceuticals Inc.
Clementia Pharmaceuticals Inc.
Not Provided
Not Provided
Clementia Pharmaceuticals Inc.
October 2017

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