ClinicalTrials.gov
ClinicalTrials.gov Menu

In-Home Evaluation of Episodic Administration of Palovarotene in Fibrodysplasia Ossificans Progressiva (FOP) Subjects

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: NCT02521792
Recruitment Status : Suspended (Subjects were enrolled into a different Phase 2 study (PVO-1A-202, NCT02279095).)
First Posted : August 13, 2015
Last Update Posted : November 17, 2017
Sponsor:
Information provided by (Responsible Party):
Clementia Pharmaceuticals Inc.

Brief Summary:
Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by painful, recurrent episodes of soft tissue swelling (flare-ups) that result in abnormal bone formation (heterotopic ossification or HO) in muscles, tendons, and ligaments. Flare-ups begin early in life and may occur spontaneously or after soft tissue trauma, vaccinations, or influenza infections. Recurrent flare-ups progressively restrict movement by locking joints leading to cumulative loss of function and disability. Mouse models of FOP have demonstrated the ability of retinoic acid receptor gamma (RARγ) agonists such as palovarotene to prevent HO following injury. This 36-month study will evaluate the long-term safety and efficacy of episodic treatment with palovarotene for flare-ups in FOP subjects who successfully complete two flare-up treatment periods (6 weeks duration) and two follow-up periods (6 weeks duration) in Study PVO-1A-202.

Condition or disease Intervention/treatment Phase
Fibrodysplasia Ossificans Progressiva Drug: Palovarotene Phase 2

Detailed Description:

The objectives of this Phase 2, open-label, multicenter, single-arm study are:

  • To evaluate the long-term safety and efficacy of prior palovarotene treatment over 36 months in FOP subjects who completed Study PVO-1A-202
  • To evaluate the safety and efficacy of palovarotene in FOP subjects experiencing new, distinct flare-ups during the 36-month follow-up period.

The follow-up portion of the study will consist of a Screening visit that will correspond to the last day (Study Day 84) of Study PVO-1A-202 and bi-annual assessments at Months 6, 12, 18, 24, 30, and 36.

Subjects experiencing a new, distinct flare-up during the 36-month follow-up will be evaluated and if eligible, receive palovarotene at the weight-adjusted equivalent of 10 mg for 14 days followed by 5 mg for at least 28 days. Any subject who received a lower dosing regimen due to tolerability issues during Study PVO-1A-202 will receive that tolerated dose.

For each flare-up there will be two periods:

  1. A Screening period to occur within 7 days of the start of a new, distinct flare-up. The first dose of palovarotene will be taken within 10 days of the flare-up onset to allow for shipment of study medication to the subject's home.
  2. A treatment period of at least 6 weeks duration. Subjects experiencing a new, distinct flare-up will be evaluated

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, In-Home, Safety and Efficacy Evaluation of Episodic Administration of Open-Label Palovarotene in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)
Study Start Date : January 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: Palovarotene
The protocol is open only to the subjects who completed Clementia Study PVO-1A-202. Eligible subjects will receive a weight-based equivalent dose of palovarotene 10 mg once daily for 14 days, followed by 5 mg once daily for 28 days. Should treatment be extended beyond 6 weeks, a weight-based equivalent dose of 5 mg will be administered in 2-week increments.
Drug: Palovarotene
Palovarotene will be taken orally once daily at approximately the same time each day. Powder filled hard gelatin capsules may be opened and the contents added onto specific food.




Primary Outcome Measures :
  1. Safety of palovarotene as assessed by the incidence of treatment-emergent adverse events (including those known to be associated with retinoids) and serious adverse events monitored throughout the treatment period. [ Time Frame: Treatment period (up to 36 months) ]

Secondary Outcome Measures :
  1. Global assessment of movement by category as determined by a subject/proxy completed questionnaire [ Time Frame: Every 6 weeks, end of treatment (an expected average of 6 weeks), and 6 weeks after end of treatment ]
  2. Change from baseline in Cumulative Analogue Joint Involvement Scale (CAJIS) for FOP [ Time Frame: Study screening, every 6 months during follow-up; Flare-up screening and every 6 weeks, end of treatment (an expected average of 6 weeks), and 6 weeks after end of treatment ]
  3. Change from baseline in extent of heterotopic ossification by whole body low-dose computerized tomography (CT) scan [ Time Frame: Study screening and 36 months ]
  4. Change from baseline in extent of heterotopic ossification by whole body dual-energy x-ray absorptiometry (DEXA) scan [ Time Frame: Study screening and 36 months ]
  5. Change from baseline in pain at flare-up site using numeric rating scale (NRS) or Faces Pain Scale-Revised (FPS-R) [ Time Frame: Flare-up screening, every 2 weeks, end of treatment (an expected average of 6 weeks), and 6 weeks after end of treatment ]
  6. Change from baseline in swelling at flare-up site using numeric rating scale (NRS) [ Time Frame: Flare-up screening, every 2 weeks, end of treatment (an expected average of 6 weeks), and 6 weeks after end of treatment ]
  7. Change from baseline in physical function using the FOP-Physical Function Questionnaire (FOP-PFQ) [ Time Frame: Study screening, every 6 months during follow-up. Flare-up screening, every 6 weeks on study drug, end of treatment (an expected average of 6 weeks), and 6 weeks after end of treatment ]
  8. Change from baseline in physical and mental health using PROMIS Global Health Scale [ Time Frame: Study screening, every 6 months during follow-up. Flare-up screening, every 6 weeks on study drug, end of treatment (an expected average of 6 weeks), 6 weeks after end of treatment. ]
  9. Duration of active, symptomatic flare-up as assessed by subject and Investigator [ Time Frame: Flare-up screening, after 6 weeks on study drug, every 2 weeks after week 6 until flare-up resolution ]
  10. Use of assistive devices and adaptations for daily living [ Time Frame: Study screening, every 6 months during follow-up. Flare-up screening, 6 weeks after end of treatment (an expected average treatment of 6 weeks), and 6-month intervals for duration of study ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

For study enrollment

  • Completed Study PVO-1A-202 having been treated with palovarotene (ie, 6 weeks on-treatment and 6-weeks follow-up) for two flare-ups.
  • Written, signed, and dated informed consent or age-appropriate subject/parent assent (this must be performed according to local regulations).

For treatment with palovarotene for subsequent flare-ups

  • Symptomatic onset of a new, distinct flare-up within 10 days of the first dose of study drug. Symptoms must be reported by the subject, be consistent with their previous flare-ups, and include a subject‑reported onset date. The flare-up must be confirmed by the physician at screening via telephone contact and/or video-conferencing.
  • Females of child-bearing potential (FOCBP) must have a negative blood (or urine) pregnancy test (with sensitivity of at least 50 mIU/mL) prior to administration of palovarotene. Male and FOCBP subjects must agree to remain abstinent during treatment and for 1 month after treatment or, if sexually active, to use two highly effective methods of birth control during and for 1 month after treatment. Additionally, sexually active FOCBP subjects must already be using two highly effective methods of birth control 1 month before treatment is to start. Specific risk of the use of retinoids during pregnancy, and the agreement to remain abstinent or use two highly effective methods of birth control will be clearly defined in the informed consent, and the subject or legally authorized representatives (eg, parents, caregivers, or legal guardians) must specifically sign this section.
  • Subjects must be accessible for treatment with palovarotene and follow-up.

Exclusion Criteria:

For study enrollment

  • 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.

For treatment with palovarotene for subsequent flare-ups:

  • Weight <20 kg.
  • The flare-up is at a completely ankylosed joint.
  • Intercurrent non-healed fracture at any location.
  • If currently using vitamin A or beta carotene, multivitamins containing vitamin A or beta carotene, or herbal preparations, fish oil, and unable or unwilling to discontinue use of these products during palovarotene treatment.
  • Exposure to synthetic oral retinoids in the past 30 days prior to screening (signature of the informed consent or age-appropriate subject assent).
  • Concurrent treatment with tetracycline or any tetracycline derivatives due to the potential increased risk of pseudotumor cerebri
  • History of allergy or hypersensitivity to retinoids or lactose.
  • Female subjects who are breastfeeding.
  • Subjects with uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, clinically significant abnormal laboratory findings, or other significant disease.
  • Simultaneous participation in another interventional clinical research study within the past 4 weeks (except for Study PVO-1A-202).
  • Subjects experiencing suicidal ideation (type 4 or 5) or any suicidal behavior within the past month prior to Screening as defined by the Columbia Suicide Severity Rating Scale.
  • 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 ClinicalTrials.gov identifier (NCT number): NCT02521792


Locations
United States, California
University of California San Francisco, Division of Endocrinology and Metabolism
San Francisco, California, United States, 94143
United States, Pennsylvania
University of Pennsylvania, Center for Research in FOP & Related Disorders
Philadelphia, Pennsylvania, United States, 19104
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 University of Pennsylvania, Center for Research in FOP & Related Disorders
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 The Royal National Orthopaedic Hospital, Brockley Hill

Additional Information:
Publications:
Responsible Party: Clementia Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02521792     History of Changes
Other Study ID Numbers: PVO-1A-203
First Posted: August 13, 2015    Key Record Dates
Last Update Posted: November 17, 2017
Last Verified: November 2017

Keywords provided by Clementia Pharmaceuticals Inc.:
Fibrodysplasia Ossificans Progressiva
Myositis Ossificans Progressiva
Open-label 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
FOP

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