Trial record 3 of 7 for:    palovarotene

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03312634
Recruitment Status : Recruiting
First Posted : October 18, 2017
Last Update Posted : March 22, 2018
Information provided by (Responsible Party):
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. 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 : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
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)
Actual Study Start Date : November 28, 2017
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : November 2020

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 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 :
  1. Subjects with New HO [ Time Frame: Screening, every 6 months up to 2 years ]
    The proportion of subjects with any new HO.

  2. 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.

  3. Subjects with Flare-Ups [ Time Frame: Up to 2 years ]
    The proportion of subjects reporting flare-ups.

  4. Rate of Flare-Ups [ Time Frame: Up to 2 years ]
    The rate of flare-ups per subject-month exposure.

  5. Incidence of Adverse Events [ Time Frame: Up to 2 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 2 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 2 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 2 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, Senior)
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.
  • 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.

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 identifier (NCT number): NCT03312634

Contact: Clinical Trials Information 1-800-750-8710
Contact: Clinical Trials Information

United States, California
University of California San Francisco, Division of Endocrinology and Metabolism Recruiting
San Francisco, California, United States, 94143
Contact: Tea Chan    415-316-8308   
Principal Investigator: Edward Hsiao, MD, PhD         
Sub-Investigator: Umesh Masharani, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Edna Mancilla, MD    215-590-3174   
Principal Investigator: Edna Mancilla, MD         
Sub-Investigator: Michael Levine, MD         
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Katherine S. Toder, CCRC    215-294-9144   
Principal Investigator: Mona Al Mukaddam, MD, MS         
Sub-Investigator: Frederick Kaplan, MD         
Canada, Ontario
Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: Irene Ho    416-340-3680   
Contact: Suzanne Cohen    416-340-4850   
Principal Investigator: Angela Cheung, MD, PhD         
Sub-Investigator: Lianne Tile, MD         
Groupe Hospitalier Necker Enfants Malades Recruiting
Paris, France, 75015
Contact: Genevieve Baujat, MD    331 44 49 51 53   
Principal Investigator: Genevieve Baujat, MD         
Sub-Investigator: Caroline Michot, MD         
Sub-Investigator: Philippe Blakime Aalem, MD         
Sub-Investigator: Breton Sylvain, MD         
Hospital Universitari i Politècnic La Fe, Unidad de Reumatología Pediatrica Recruiting
Valencia, Avinguda De Fernando Abril Martorell, Nº 106, Spain, 46026
Contact: Inmaculada Calvo, MD, PhD    0034 96 124 4792   
Principal Investigator: Inmaculada Calvo, MD, PhD         
Sub-Investigator: Maria Isabel Gonzalez, MD         
Sub-Investigator: Berta Lopez, MD         
Sub-Investigator: Miguel Martí, MD, PhD         
Norrlands Universitetssjukhus Recruiting
Umeå, Sweden, SE-90185
Contact: Staffan Berglund, MD, PhD    +46 90 7850225   
Principal Investigator: Staffan Berglund, MD, PhD         
Sub-Investigator: Maria Björmsjö, MD         
Sponsors and Collaborators
Clementia Pharmaceuticals Inc.

Additional Information:
Responsible Party: Clementia Pharmaceuticals Inc. Identifier: NCT03312634     History of Changes
Other Study ID Numbers: PVO-1A-301
First Posted: October 18, 2017    Key Record Dates
Last Update Posted: March 22, 2018
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.:
Interventional study
Clinical trial phase 3
Efficacy and safety
Heterotopic ossification
Retinoic acid receptor agonist
Retinoic acid receptor gamma agonist
Myositis Ossificans Progressiva
Munchmeyer's Disease

Additional relevant MeSH terms:
Myositis Ossificans
Muscular Diseases
Musculoskeletal Diseases