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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.
  Purpose
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 Intervention Phase
Fibrodysplasia Ossificans Progressiva Drug: Palovarotene Phase 3

Study Type: Interventional
Study Design: 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
Official Title: MOVE TRIAL: A Phase 3, Efficacy and Safety Study of Oral Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)

Resource links provided by NLM:


Further study details as provided by Clementia Pharmaceuticals Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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.


Estimated Enrollment: 80
Anticipated Study Start Date: November 2017
Estimated Study Completion Date: November 2020
Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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).

  Eligibility

Information from the National Library of Medicine

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

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.
  Contacts and Locations
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


Contacts
Contact: Clinical Trials Information 1-800-750-8710 ClinicalTrials@clementiapharma.com
Contact: Clinical Trials Information

Sponsors and Collaborators
Clementia Pharmaceuticals Inc.
  More Information

Additional Information:
Publications:
Responsible Party: Clementia Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT03312634     History of Changes
Other Study ID Numbers: PVO-1A-301
First Submitted: October 9, 2017
First Posted: October 18, 2017
Last Update Posted: November 16, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Clementia Pharmaceuticals Inc.:
Myositis Ossificans Progressiva
FOP
Interventional study
Clinical trial phase 3
Efficacy and safety
Heterotopic ossification
Flare-up
Palovarotene
Retinoic acid receptor agonist
Retinoic acid receptor gamma agonist
Clementia
Munchmeyer's Disease

Additional relevant MeSH terms:
Myositis Ossificans
Myositis
Muscular Diseases
Musculoskeletal Diseases