- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02521792
In-Home Evaluation of Episodic Administration of Palovarotene in Fibrodysplasia Ossificans Progressiva (FOP) Subjects
A Phase 2, In-Home, Safety and Efficacy Evaluation of Episodic Administration of Open-Label Palovarotene in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The primary objective of this Phase 2, open-label, multicenter, single-arm, extension study is to investigate the safety and efficacy of episodic treatment with palovarotene in FOP subjects with flare-ups.
Secondary objectives are:
The effect of episodic treatment of flare-ups with palovarotene on range of motion (ROM) as assessed by the subject global assessment of movement.
- The effect of episodic treatment of flare-ups with palovarotene on ROM as assessed by the Cumulative Analogue Joint Involvement Scale for FOP (CAJIS) for subjects with video-conferencing capability.
- The effect of episodic treatment of flare-ups with palovarotene on the total burden of heterotopic ossification (HO) as assessed by low-dose whole body computerized tomography (WBCT), excluding the head; and whole body dual energy x-ray absorptiometry (DEXA).
- The effect of episodic treatment of flare-ups with palovarotene on physical function using age-appropriate forms of the FOP-Physical Function Questionnaire (FOP-PFQ).
- The effect of episodic treatment of flare-ups with palovarotene on physical and mental health using age appropriate forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale.
- The effects of episodic treatment of flare-ups with palovarotene on pain and swelling associated with the flare-up using numeric rating scales (NRS) or the Faces Pain Scale-Revised (FPS-R) in subjects under 8 years of age.
- The use of assistive devices and adaptations for daily living by FOP subjects.
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:
- 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.
- A treatment period of at least 6 weeks duration. Subjects experiencing a new, distinct flare-up will be evaluated
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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San Francisco, California, United States, 94143
- University of California San Francisco, Division of Endocrinology and Metabolism
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania, Center for Research in FOP & Related Disorders
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Time Frame: Day 1 until 6 weeks after the end of treatment (an expected average treatment of 6 weeks). Assessed until data cut-off for study termination (maximum of 35 days).
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The primary endpoint was the safety of palovarotene as assessed by the incidence of TEAEs (including those known to be associated with retinoids) and serious adverse event (SAEs) monitored throughout the treatment period.
TEAEs were adverse events reported during treatment with palovarotene or within 6 weeks after the end of treatment.
Day 1 was the first day that study drug was administered for a flare-up.
The number of subjects experiencing at least one TEAE or treatment-emergent SAE are presented.
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Day 1 until 6 weeks after the end of treatment (an expected average treatment of 6 weeks). Assessed until data cut-off for study termination (maximum of 35 days).
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Subject Global Assessment of Movement as Determined by a Subject Completed Questionnaire, or Proxy Completed Questionnaire in Subjects Under 8 Years of Age
Time Frame: Every 6 weeks while on study drug, at the end of treatment (should treatment be extended beyond 6 weeks), and 6 weeks after the end of treatment.
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Every 6 weeks while on study drug, at the end of treatment (should treatment be extended beyond 6 weeks), and 6 weeks after the end of treatment.
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Change From Baseline in Cumulative Analogue Joint Involvement Scale for FOP as Assessed by the Investigator Using Remote Video-conferencing
Time Frame: Baseline (flare-up screening), every 6 weeks while on study drug, at the end of treatment (should treatment be extended beyond 6 weeks), and 6 weeks after the end of treatment.
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Baseline (flare-up screening), every 6 weeks while on study drug, at the end of treatment (should treatment be extended beyond 6 weeks), and 6 weeks after the end of treatment.
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Change From Baseline in Extent of Heterotopic Ossification (HO) by Whole Body Low-dose Computerized Tomography (CT) Scan, Excluding the Head
Time Frame: Baseline (final visit for Study PVO-1A-202/Part A) and at end of study (36 months).
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Baseline (final visit for Study PVO-1A-202/Part A) and at end of study (36 months).
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Change From Baseline in Extent of HO by Whole Body Dual Energy X-ray Absorptiometry (DEXA) Scan
Time Frame: Baseline (screening/enrollment visit) and at end of study (36 months).
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Baseline (screening/enrollment visit) and at end of study (36 months).
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Change From Baseline in Pain and Swelling at the Flare-up Site Using Numeric Rating Scales, or Faces Pain Scale-Revised in Subjects Under 8 Years of Age
Time Frame: Baseline (flare-up screening), every 2 weeks while on study drug, at the end of treatment (should treatment be extended beyond 6 weeks), and 6 weeks after the end of treatment.
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Baseline (flare-up screening), every 2 weeks while on study drug, at the end of treatment (should treatment be extended beyond 6 weeks), and 6 weeks after the end of treatment.
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Change From Baseline in Physical Function Using Age-appropriate Forms of the FOP-Physical Function Questionnaire
Time Frame: Baseline (flare-up screening), every 6 weeks while on study drug, at the end of treatment (should treatment be extended beyond 6 weeks), and 6 weeks after the end of treatment, and 6-month intervals for duration of study.
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Baseline (flare-up screening), every 6 weeks while on study drug, at the end of treatment (should treatment be extended beyond 6 weeks), and 6 weeks after the end of treatment, and 6-month intervals for duration of study.
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Change From Baseline in Physical and Mental Health Using Age-appropriate Forms of the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Scale
Time Frame: Baseline (flare-up screening), every 6 weeks while on study drug, at the end of treatment (should treatment be extended beyond 6 weeks), 6 weeks after the end of treatment, and 6-month intervals for duration of study.
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Baseline (flare-up screening), every 6 weeks while on study drug, at the end of treatment (should treatment be extended beyond 6 weeks), 6 weeks after the end of treatment, and 6-month intervals for duration of study.
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Duration of Active, Symptomatic Flare-up as Assessed by the Subject and the Investigator
Time Frame: Baseline (flare-up screening), after 6 weeks on study drug, and every 2 weeks after Week 6 until flare-up resolution.
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Baseline (flare-up screening), after 6 weeks on study drug, and every 2 weeks after Week 6 until flare-up resolution.
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Change From Baseline in the Use of Assistive Devices and Adaptations for Daily Living by FOP Subjects
Time Frame: Baseline (flare-up screening), 6 weeks after the end of treatment, and 6-month intervals for duration of study.
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Baseline (flare-up screening), 6 weeks after the end of treatment, and 6-month intervals for duration of study.
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Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PVO-1A-203
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Fibrodysplasia Ossificans Progressiva
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IpsenActive, not recruitingFibrodysplasia Ossificans Progressiva (FOP)United States, France, Australia, Argentina, Italy, Canada, Sweden, United Kingdom, Brazil, Spain
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Incyte CorporationRecruitingFibrodysplasia Ossificans Progressiva (FOP)United States, France, Korea, Republic of, Spain, Italy, United Kingdom, Russian Federation, China, Australia, Brazil, Mexico, New Zealand, Argentina, Canada, Netherlands, Turkey, Chile, Germany, South Africa, Portugal
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Clementia Pharmaceuticals Inc.CompletedFibrodysplasia Ossificans ProgressivaUnited States, Canada, France, Australia, Argentina, Brazil, Italy, Japan, Spain, Sweden, United Kingdom
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The International FOP AssociationRecruitingFibrodysplasia Ossificans Progressiva (FOP)United States
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Regeneron PharmaceuticalsCompletedFibrodysplasia Ossificans Progressiva (FOP)United States
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IpsenNot yet recruiting
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Clementia Pharmaceuticals Inc.IpsenRecruitingFibrodysplasia Ossificans ProgressivaUnited States, Korea, Republic of, Belgium, China, Sweden, France, Japan, Argentina, Australia, Brazil, Canada, Italy, Spain, United Kingdom, Mexico, Colombia, Netherlands, Germany, Portugal
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Daiichi Sankyo Co., Ltd.CompletedFibrodysplasia Ossificans ProgressivaJapan
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Clementia Pharmaceuticals Inc.CompletedFibrodysplasia Ossificans ProgressivaUnited States
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Regeneron PharmaceuticalsCompletedFibrodysplasia Ossificans ProgressivaUnited States, Spain, Canada, France, Poland, Italy, Netherlands, United Kingdom
Clinical Trials on Palovarotene
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Clementia Pharmaceuticals Inc.Completed
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Clementia Pharmaceuticals Inc.CompletedFibrodysplasia Ossificans ProgressivaUnited States, Argentina, Australia, France, United Kingdom
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Clementia Pharmaceuticals Inc.TerminatedExostoses, Multiple HereditaryUnited States, Spain, Canada, Japan, Italy, Portugal, United Kingdom, Turkey, Australia, Belgium, France, Netherlands
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IpsenActive, not recruitingFibrodysplasia Ossificans Progressiva (FOP)United States, France, Australia, Argentina, Italy, Canada, Sweden, United Kingdom, Brazil, Spain
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Clementia Pharmaceuticals Inc.CompletedFibrodysplasia Ossificans ProgressivaFrance
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Clementia Pharmaceuticals Inc.IpsenCompleted
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Clementia Pharmaceuticals Inc.CompletedFibrodysplasia Ossificans ProgressivaUnited States, Canada, France, Australia, Argentina, Brazil, Italy, Japan, Spain, Sweden, United Kingdom
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Clementia Pharmaceuticals Inc.CompletedFibrodysplasia Ossificans ProgressivaUnited States, France, United Kingdom
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Clementia Pharmaceuticals Inc.CompletedFibrodysplasia Ossificans ProgressivaUnited States