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Trial record 8 of 29 for:    fop

An Open-Label Extension Study of Palovarotene Treatment in 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.
ClinicalTrials.gov Identifier: NCT02279095
Recruitment Status : Active, not recruiting
First Posted : October 30, 2014
Last Update Posted : October 10, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
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. In this study, the ability of palovarotene to prevent HO formation will be evaluated.

Condition or disease Intervention/treatment Phase
Fibrodysplasia Ossificans Progressiva Drug: Palovarotene dose level 1 Drug: Palovarotene dose level 2 Drug: Palovarotene dose level 3 Drug: Palovarotene dose level 4 Phase 2

Detailed Description:

The main objective of this Phase 2, multicenter, open-label study is to evaluate the safety and efficacy of different palovarotene dosing regimens in subjects with FOP.

In Part A, all subjects who completed Study PVO-1A-201 and enrolled into the current study received daily treatment with open-label palovarotene for an eligible flare-up at a dose of 10 mg for 14 days, followed by 5 mg for 28 days (or the weight-based equivalent). Part A is completed.

In Part B, subjects with at least 90% skeletal maturity were treated with 5 mg palovarotene on a daily basis (ie, chronically). In the event of an eligible flare-up, all subjects received 20 mg palovarotene daily for 28 days, followed by 10 mg for 56 days (dosing was weight-based in subjects who were skeletally immature). Dosing could be extended if the flare-up was not resolved by Flare-up Day 84 and continued until the flare-up resolved. Dose reduction, as directed by the Investigator, occurred in the event of intolerable side effects. The duration of Part B is up to 24 months.

In Part C, the dosing regimens implemented in Part B will continue except that subjects with less than 90% skeletal maturity will now receive chronic daily administration of palovarotene (5 mg, or the weight-based equivalent). The assessment of HO will occur every 12 months using low-dose, whole body computed tomography (WBCT), excluding head; other efficacy and safety outcomes will be evaluated remotely every 3 months, or monthly during flare-up based treatment. The duration of Part C is 36 months.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label Extension, Efficacy and Safety Study of a RARγ Specific Agonist (Palovarotene) in the Treatment of Preosseous Flare-ups in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)
Study Start Date : October 2014
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021


Arms and Interventions

Arm Intervention/treatment
Experimental: Palovarotene dose level 1 (completed)
Subjects received weight-adjusted doses of palovarotene equivalent to 10 mg once daily for 14 days, followed by 5 mg once daily for 28 days for an eligible flare-up (Part A).
Drug: Palovarotene dose level 1
Palovarotene was taken orally once daily at approximately the same time each day.
Experimental: Palovarotene dose level 2
Subjects with at least 90% skeletal maturity received 5 mg palovarotene once daily for up to 24 months; and 20 mg palovarotene for 28 days, followed by 10 mg for 56 days for eligible flare-ups (Part B).
Drug: Palovarotene dose level 2
Palovarotene will be taken orally once daily at approximately the same time each day.
Experimental: Palovarotene dose level 3
Subjects with less than 90% skeletal maturity received weight-adjusted doses of 20 mg palovarotene for 28 days, followed by 10 mg for 56 days for eligible flare-ups (Part B).
Drug: Palovarotene dose level 3
Palovarotene will be taken orally once daily at approximately the same time each day.
Experimental: Palovarotene dose level 4
All subjects will receive 5 mg palovarotene once daily for up to 36 months; and 20 mg palovarotene for 28 days, followed by 10 mg for 56 days for eligible flare-ups (Part C). Doses are adjusted for weight in skeletally immature subjects
Drug: Palovarotene dose level 4
Palovarotene will be taken orally once daily at approximately the same time each day.


Outcome Measures

Primary Outcome Measures :
  1. Change in New HO Volume [ Time Frame: Screening, every 12 months up to 60 months ]
    Annualized change in new HO volume as assessed by low-dose, WBCT (excluding head).


Secondary Outcome Measures :
  1. Subjects with New HO [ Time Frame: Baseline, every 12 months up to 60 months ]
    The proportion of subjects with any new HO.

  2. Range of Motion [ Time Frame: Baseline, every 6 months up to 60 months ]
    Change from baseline in range of motion as assessed by the Cumulative Analogue Joint Involvement Scale for FOP (CAJIS).

  3. FOP-Physical Function Questionnaire [ Time Frame: Baseline, every 6 months up to 60 months ]
    Change from baseline in physical function using age-appropriate forms of the FOP-Physical Function Questionnaire (PFQ).

  4. PROMIS Global Health Scale [ Time Frame: Baseline, every 6 months up to 60 months ]
    Change from baseline in mental and/or physical health function for subjects using age-appropriate forms of the PROMIS Global Health Scale.

  5. Incidence of Adverse Events [ Time Frame: every month up to 60 months ]
    Monitor adverse events.

  6. Pharmacokinetics of Palovarotene [ Time Frame: Pre-dose and 3, 6, 10, and 24 hours post-dose ]
    Steady-state pharmacokinetics assessed during treatment with 10 and 20 mg palovarotene.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Completion of Study PVO-1A-202/Part B.
  • Written, signed, and dated informed consent and, for subjects who are minors, age-appropriate subject assent (performed according to local regulations).
  • Accessible for treatment with palovarotene and follow-up (able and willing to travel to a site for the initial and all follow-up clinic visits).
  • Able to undergo low-dose, WBCT scan, excluding head.

Exclusion Criteria:

  • 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.
  • Amylase or lipase >2x above the upper limit of normal or with a history of pancreatitis.
  • Elevated aspartate aminotransferase or alanine aminotransferase >2.5x the upper limit of normal.
  • Fasting triglycerides >400 mg/dL with or without therapy.
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): NCT02279095


Locations
United States, California
University of California San Francisco, Division of Endocrinology and Metabolism
San Francisco, California, United States, 94143
United States, Minnesota
Mayo Clinic, Department of Medicine
Rochester, Minnesota, United States, 55905
United States, Pennsylvania
University of Pennsylvania, Center for FOP & Related Bone Disorders
Philadelphia, Pennsylvania, United States, 19104
Argentina
Hospital Italiano de Buenos Aires, Department of Pediatrics
Buenos Aires, Argentina
Australia, Queensland
Queensland University of Technology (QUT) Institute of Health and Biomedical Innovation (IHBI)
Woolloongabba, Queensland, Australia, 4102
France
Hôpital Necker-Enfants Malades, Department of Genetics
Paris, France
United Kingdom
The Royal National Orthopaedic Hospital, Brockley Hill
Stanmore, Middlesex, United Kingdom, HA7 4LP
Sponsors and Collaborators
Clementia Pharmaceuticals Inc.
Investigators
Principal Investigator: Robert J Pignolo, MD, PhD Mayo Clinic, Department of Medicine
Principal Investigator: Edward Hsiao, MD, PhD University of California San Francisco, Division of Endocrinology and Metabolism
Principal Investigator: Genevieve Baujat, MD Hôpital Necker-Enfants Malades, Department of Genetics
Principal Investigator: Richard Keen, BSc, PhD, MD The Royal National Orthopaedic Hospital, Brockley Hill
Principal Investigator: Carmen L De Cunto, MD Hospital Italiano de Buenos Aires
Principal Investigator: Mona Al Mukaddam, MD, MS, CCD University of Pennsylvania
Principal Investigator: Matthew Brown, MD Queensland University of Technology (QUT) Institute of Health and Biomedical Innovation (IHBI)
More Information

Additional Information:
Publications:
Responsible Party: Clementia Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02279095     History of Changes
Other Study ID Numbers: PVO-1A-202
First Posted: October 30, 2014    Key Record Dates
Last Update Posted: October 10, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Clementia Pharmaceuticals Inc.:
Fibrodysplasia Ossificans Progressiva
Myositis Ossificans Progressiva
FOP
Open-label extension study
Clinical trial Phase 2
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