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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   43216   clinical trials with a EudraCT protocol, of which   7153   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2021-002244-70
    Sponsor's Protocol Code Number:CLIN-60120-452
    National Competent Authority:Sweden - MPA
    Clinical Trial Type:EEA CTA
    Trial Status:
    Date on which this record was first entered in the EudraCT database:2021-10-25
    Trial 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 ConcernedSweden - MPA
    A.2EudraCT number2021-002244-70
    A.3Full title of the trial
    Rollover Study; Multicentre, Phase III, Open-label Study to Further Evaluate the Safety and Efficacy of Palovarotene Capsules in Male and Female Participants Aged ≥14 Years with Fibrodysplasia Ossificans Progressiva (FOP) Who Have Completed Study PVO-1A-301 or PVO-1A-202/PVO-1A-204 and May Benefit from Palovarotene Therapy.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Rollover Study to Further Evaluate the Safety and Efficacy of Palovarotene Capsules in Male and Female Participants Aged ≥14 Years with Fibrodysplasia Ossificans Progressiva (FOP) Who Have Completed the Relevant Parent Studies.
    A.3.2Name or abbreviated title of the trial where available
    PIVOINE
    A.4.1Sponsor's protocol code numberCLIN-60120-452
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorIpsen Pharma SAS
    B.1.3.4CountryFrance
    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 supportIpsen Pharma SAS
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIPSEN Pharma SAS
    B.5.2Functional name of contact pointMedical Affairs Clinical Operations
    B.5.3 Address:
    B.5.3.1Street Address65, quai Georges Gorse
    B.5.3.2Town/ cityBoulogne-Billancourt
    B.5.3.3Post code92100
    B.5.3.4CountryFrance
    B.5.4Telephone number+337 6156 64 63
    B.5.6E-mailBayane.Tannir@ipsen.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 IPN60120
    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.3.9.2Current sponsor codeIPN60120
    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 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
    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)
    E.1.1.1Medical condition in easily understood language
    Fibrodysplasia Ossificans Progressiva
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    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 further evaluate the safety of palovarotene in adult and paediatric participants with FOP.
    E.2.2Secondary objectives of the trial
    • To describe range of motion, as assessed by the Cumulative Analogue Joint Involvement Scale (CAJIS) for FOP, at the Inclusion Visit and over time under palovarotene treatment.
    • To describe the use of assistive devices and adaptations for daily living by FOP participants, at the Inclusion Visit and over time under palovarotene treatment.
    • To describe physical function, using the adult form of the FOP Physical Function Questionnaire, at the Inclusion Visit and over time under palovarotene treatment.
    • To describe the FOP healthcare utilization in patients with FOP.
    • To describe the parameters of lung function at the Inclusion Visit and over time under palovarotene treatment.
    • To describe physical and mental health, using the adult form of the Patient Reported Outcomes Measurement Information System Global Health Scale, at the Inclusion Visit and over time under palovarotene treatment.

    Please refer to protocol for other secondary objectives.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Participants are eligible to be included in the study only if all of the following criteria apply:
    1. Participant has completed the EOS or End of Treatment Visit of Study PVO-1A-301 or PVO-1A-202 (PVO-1A-202 Parts C and D correspond to Study PVO-1A-204 in France) and did not previously withdraw consent from any of the parent studies to be eligible for Study CLIN-60120-452.
    2. In the investigator’s judgment, the participant may benefit from continued participation in a palovarotene study.

    Age
    3. Participant must be ≥14 years of age (aligned with the age of treated participants in the ongoing parent studies PVO-1A-301 and PVO-1A-202/PVO-1A-204) and qualify as 100% skeletally mature (if <18 years, based on assessments carried out at parent EOS Visit; if ≥18 years, automatically considered 100% skeletally mature) or have reached final adult height based on investigator’s assessment*, at the time the Study CLIN60120-452 informed consent is signed.
    *The above criteria can be reached at any point after parent study end for the participant to be eligible for Study CLIN-60120-452, as long as it is prior to palovarotene becoming reimbursed in the country where the study is being conducted.

    Sex
    4. Male, or female who is not pregnant or breastfeeding, and has met all of the following conditions:
    • Females of child-bearing potential (FOCBP) (defined in Section 10.2.1 of the protocol) must have a negative blood or urine pregnancy test (with sensitivity of at least 50 mIU/mL) prior to administration of palovarotene;
    • FOCBP must agree to remain abstinent from heterosexual sex during treatment and for one month after treatment or, if sexually active, to use two effective methods of birth control (described in Section 10.2.2 of the protocol) during and for one month after treatment;
    Additionally, sexually active FOCBP must already be using two effective methods of birth control one month before treatment is to start;
    • Specific risk of the use of retinoids during pregnancy, and the agreement to remain abstinent or use two effective methods of birth control will be clearly defined in the informed consent and the participant or legally authorised representatives (e.g. parents, caregivers or legal guardians) must specifically sign this section.
    Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

    Informed Consent and Assent
    5. Capable of giving signed informed consent or providing assent as described in Section 10.1.3 of the protocol.
    E.4Principal exclusion criteria
    Participants will not be included in the study if any of the following criteria apply:

    Medical conditions
    1. History of allergy or hypersensitivity to retinoids, gelatin, lactose (note that lactose intolerance is not exclusionary) or palovarotene, or unresponsiveness to prior treatment with palovarotene.
    2. Uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, or other significant disease.
    3. Symptomatic vertebral fracture.
    4. Any other medical condition/clinically significant abnormalities that would expose the participant to undue risk or interfere with study assessments.
    5. Amylase or lipase >2× above the upper limit of normal (ULN) or with a history of chronic pancreatitis.
    6. Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5× ULN.
    7. Fasting triglycerides >400 mg/dL with or without therapy.
    8. Suicidal ideation (type 4 or 5) or any suicidal behaviour at Inclusion Visit as defined by the Columbia-Suicide Severity Rating Scale (C-SSRS).

    Prior/concomitant therapy
    9. Current use of 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.
    10. Exposure to synthetic oral retinoids other than palovarotene within 4 weeks of the Inclusion Visit.
    11. Concurrent treatment with tetracycline or any tetracycline derivatives due to the potential increased risk of pseudotumor cerebri.
    12. Use of concomitant medications that are strong inhibitors or inducers of cytochrome P450 (CYP450) 3A4 activity (see Section 6.8 and 10.5 of protocol); or kinase inhibitors such as imatinib.

    Other exclusion criteria
    13. Palovarotene is reimbursed in the country where the study is being conducted.
    14. Any reason that, in the opinion of the investigator, would lead to the inability of the participant and/or family to comply with the protocol.
    E.5 End points
    E.5.1Primary end point(s)
    • Incidence and description of all treatment emergent adverse events (TEAEs) whether or not they are considered as related to the study intervention;
    • Incidence and description of all serious and nonserious treatment-related TEAEs;
    • Incidence and description of all serious TEAEs, whether or not they are considered as related to the study intervention;
    • Incidence and description of all nonserious TEAEs whether or not they are considered as related to the study intervention.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At Inclusion Visit (Day 1) and then every 6 months at Follow-up Visits until End of Study or Early Withdrawal.
    E.5.2Secondary end point(s)
    • Raw values and change from the Inclusion Visit in CAJIS total score at each Follow-up Visit;
    • Raw values and shift from the Inclusion Visit in the use of assistive devices and adaptations for daily living at each Follow-up Visit;
    • Raw values and change from the Inclusion Visit in % of worst score for total score, upper extremities subscore and mobility subscore using the adult form of the FOP-PFQ for all participants, at each Follow-up Visit;
    • Type and frequency of healthcare utilization
    • Raw values and change from the Inclusion Visit in observed and % predicted FVC at each Follow-up Visit;
    • Raw values and change from the Inclusion Visit in observed and % predicted FEV1 at each Follow-up Visit;
    • Raw values and change from the Inclusion Visit in absolute and % predicted FEV1/FVC ratio at each Follow-up Visit;
    • Raw values and change from the Inclusion Visit in observed and % predicted DLCO at each Follow-up Visit;
    • Raw values and change from the Inclusion Visit in physical and mental function (mean global physical and mental health score converted into T-scores), using the adult form of the PROMIS Global Health Scale for all participants, at each Follow-up Visit;
    • Raw values and change from the Inclusion Visit in number of investigator-reported flareups, flare-up outcomes (new bone growth, restricted movement) and flare-up duration at each Follow-up Visit by body location and overall;
    • Percentage of participants with new bone growth overall and by flare-up status at each Follow-up Visit;
    E.5.2.1Timepoint(s) of evaluation of this end point
    At Inclusion Visit (Day 1) and then every 6 months at Follow-up Visits until End of Study or Early Withdrawal.
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    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.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    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
    Australia
    Brazil
    Canada
    France
    Italy
    Spain
    Sweden
    United Kingdom
    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
    Last Patient Last Visit (LPLV)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial days17
    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: 14
    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) No
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 33
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 53
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 1
    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 state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 18
    F.4.2.2In the whole clinical trial 87
    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)
    Participants may continue to receive palovarotene once it becomes reimbursed or when another access programme becomes available, or until the study end date of November 2024 is reached, whichever occurs first.
    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 Decision2021-12-06
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial Status
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