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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   43206   clinical trials with a EudraCT protocol, of which   7151   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


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    Summary
    EudraCT Number:2014-001453-17
    Sponsor's Protocol Code Number:PVO-1A-201
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-02-25
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2014-001453-17
    A.3Full title of the trial
    A Phase 2 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of a RARĪ³-Specific Agonist (Palovarotene) in the Treatment of Preosseous Flare-ups in Subjects with Fibrodysplasia Ossificans Progressiva (FOP).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The Study of an Investigational Drug, Palovarotene, in the Treatment of Preosseous Flare-ups in Subjects with Fibrodysplasia Ossificans Progressiva.
    A.4.1Sponsor's protocol code numberPVO-1A-201
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02190747
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/127/2015
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorClementia Pharmaceuticals Inc.
    B.1.3.4CountryCanada
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportClementia Pharmaceuticals Inc.
    B.4.2CountryCanada
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedpace France
    B.5.2Functional name of contact pointClinical Trials Information
    B.5.3 Address:
    B.5.3.1Street AddressLe Rhône Alpes 235, cours Lafayette
    B.5.3.2Town/ cityLyon
    B.5.3.3Post code69006
    B.5.3.4CountryFrance
    B.5.4Telephone number33437 53 09 80
    B.5.5Fax number33972 36 97 87
    B.5.6E-mailregsubmissions@medpace.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/14/1368
    D.3 Description of the IMP
    D.3.1Product namePalovarotene
    D.3.2Product code Palovarotene
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPALOVAROTENE
    D.3.9.1CAS number 410528-02-8
    D.3.9.3Other descriptive namePALOVAROTENE
    D.3.9.4EV Substance CodeSUB75998
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number1.5 to 10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/14/1368
    D.3 Description of the IMP
    D.3.1Product namePalovarotene
    D.3.2Product code Palovarotene
    D.3.4Pharmaceutical form Oral powder in sachet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPALOVAROTENE
    D.3.9.1CAS number 410528-02-8
    D.3.9.3Other descriptive namePALOVAROTENE
    D.3.9.4EV Substance CodeSUB75998
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number1.5 to 10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule, hard
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboOral powder in sachet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by painful, recurrent episodes of soft tissue swelling (flare-ups) and abnormal heterotopic ossification (HO) in muscles, tendons, and ligaments. Lesions begin in early childhood and lead to progressive ankyloses of major joints with resultant loss of movement. Prognosis is poor and median life expectancy is 40 years.
    E.1.1.1Medical condition in easily understood language
    FOP is a rare, severely disabling disease characterized by painful, recurrent episodes of soft tissue swelling (flare-ups) and abnormal heterotopic ossification in muscles, tendons, and ligaments.
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10068715
    E.1.2Term Fibrodysplasia ossificans progressiva
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the ability of different doses of palovarotene to prevent heterotopic ossification at the flare-up site in subjects with FOP as assessed by plain radiographs.
    E.2.2Secondary objectives of the trial
    •To investigate the safety of palovarotene (IP) vs placebo in FOP subjects w/flare-ups (FUps) •To evaluate (eval) effect of IP on ROM as assessed by goniometer and global assessment of movement •To eval effect of IP on physical function using age-appropriate FOP-PFQs •To eval effect of IP on physical/mental health using age-appropriate PROMIS Global Health Scales •To eval effects of IP on pain/swelling associated with FUps using NRS or FPS-R in subjects under 8 years of
    age •To eval use of assistive devices/adaptations for daily living by FOP subjects •To eval effects of IP on bone formation at the FUp site as assessed by low dose CT •To eval effects of IP on soft tissue
    swelling/cartilage formation at FUp site as assessed by MRI; or soft tissue swelling as assessed by ultrasound •To eval cartilage, bone, angiogenesis, inflammation biomarkers & explore correlations b/w changes from baseline in biomarkers & clinical efficacy •To eval PK of IP at steady-state in FOP subjects
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    •Male or female at least 6 years of age.
    •Subjects clinically diagnosed with classic FOP.
    •Symptomatic onset of a distinct flare-up within 7 days of Study Day 1 (start of study drug) and defined by the presence of at least two of six of the following symptoms: pain, soft tissue swelling, decreased ROM, stiffness, redness, and warmth. Symptoms must be reported by the subject during the pre-screening period, be consistent with their previous flare-ups, include a subject-reported onset date, and flare-up confirmed by the Investigator at the Screening visit.
    •Flare-up is at an appendicular area (upper or lower extremity), abdomen, or chest; and subject has received, is receiving, or is willing to receive treatment per standard of care, which may or may not include prednisone (2 mg/kg PO [per os] to a maximum dose of 100 mg daily) for 4 days.
    E.4Principal exclusion criteria
    •Weight <20 kg.
    •Intercurrent non-healed fracture at any location.
    •Complete immobilization of joint at site of flare-up.
    •The inability of the subject to undergo imaging assessments using plain radiographs.
    •If currently using vitamin A or beta carotene, multivitamins containing vitamin A or beta carotene, herbal preparations, fish oil, and unable or unwilling to discontinue use of these products for the duration of the study.
    •Exposure to synthetic oral retinoids in the past 30 days prior to Screening (signature of the informed consent).
    •Concurrent treatment with tetracycline due to the potential increased risk of pseudotumor cerebri.
    •History of allergy or hypersensitivity to retinoids or lactose.
    •Concomitant medications that are inhibitors or inducers of CYP450 3A4 activity.
    E.5 End points
    E.5.1Primary end point(s)
    The percentage of subject responders as defined by no or minimal new HO at the flare-up site compared with baseline as assessed by plain radiographs at Study Day 42.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The percentage of subject responders as defined by no or minimal new HO at the flare-up site compared with baseline as assessed by plain radiographs at Study Day 42.
    E.5.2Secondary end point(s)
    1. Proportion of subjects across the seven HO scores (0-6) at the flare-up site as assessed by plain radiographs at Study Days 42 and 84.
    2. Change from baseline in amount (area) of new heterotopic bone formed at the flare-up site assessed by plain radiographs at Study Days 42 and 84.
    3. Percentage of subject responders as defined by no or minimal new HO at the flare-up site as compared with baseline as assessed by plain radiographs at Study Day 84.
    4. Change from baseline in cartilage, bone, angiogenesis, and inflammation biomarkers at Study Days 14, 28, 42, and 84.
    5. Change from baseline in amount of bone formation (volume) at Study Days 42 and 84 as assessed by low dose CT scan.
    6. Presence of soft tissue swelling and/or cartilage by MRI at Study Days 42 and 84; or presence of soft tissue swelling by ultrasound (US) at Study Days 42 and 84 in subjects unable to undergo MRI.
    7. Change from baseline in active ROM measured by goniometer of the relevant joint at Study Days 42 and 84.
    8. Subject and Investigator global assessment of movement at Study Days 42 and 84.
    9. Change from baseline in pain and swelling at the flare-up site using NRS, or the FPS-R for subjects under 8 years of age, for each symptom at Study Days 14, 28, 42, 63, and 84.
    10. Change from baseline in the use of assistive devices and adaptations for daily living by FOP subjects at Study Days 42 and 84.
    11. Duration of active, symptomatic flare-up (start date and end date), as assessed by the subject and the Investigator.
    12. Change from baseline in physical function using age-appropriate forms of the FOP-PFQ at Study Days 14, 28, 42, 63, and 84.
    13. Change from baseline in physical and mental health using age-appropriate forms of the PROMIS Global Health Scales at Study Days 14, 28, 42, 63, and 84.
    14. Assessment of PK parameters at steady-state on Study Day 14, and on Study Day 28 or 42.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The various secondary endpoints will be measured at some or all of the following study days: 14, 28, 42, 63, and 84.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Duration of Treatment; Use of Assistive Devices
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA2
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days22
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days14
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 10
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 5
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 5
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 30
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state4
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 12
    F.4.2.2In the whole clinical trial 40
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Consistent with pre-study treatment, if any. In addition, subjects completing the study will be given the opportunity to enroll into an open label extension study (Study PVO-1A-202; to be submitted as a separate CTA) provided they meet eligibility requirements.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-04-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-07-07
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-05-23
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