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    Summary
    EudraCT Number:2020-002858-24
    Sponsor's Protocol Code Number:D-CA-60130-452
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-06-04
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2020-002858-24
    A.3Full title of the trial
    A Phase 2, two-part, placebo-controlled, parallel-group, double-blind study to assess the efficacy and safety of 2 dosage regimens of oral IPN60130 for the treatment of fibrodysplasia ossificans progressiva in male and female participants 5 years of age and older
    Studio di fase 2, in due parti, a gruppi paralleli, in doppio cieco e controllato con placebo per valutare l’efficacia e la sicurezza di 2 regimi di dosaggio di IPN60130 per via orale per il trattamento della fibrodisplasia ossificante progressiva in partecipanti di sesso maschile e femminile con un’età uguale o maggiore di 5 anni
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study assessing the efficacy and safety of an investigational drug called
    IPN60130 for the treatment of fibrodysplasia ossificans progressiva in
    participants aged 5 years of age and older
    Studio che valuta l’efficacia e la sicurezza di un farmaco sperimentale detto IPN60130 per il trattamento della fibrodisplasia ossificante progressiva in partecipanti con età pari o superiore a 5 anni
    A.3.2Name or abbreviated title of the trial where available
    -
    -
    A.4.1Sponsor's protocol code numberD-CA-60130-452
    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 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, an Ipsen Company
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationClementia Pharmaceuticals Inc, an Ipsen Company
    B.5.2Functional name of contact pointEric SOLIMAN
    B.5.3 Address:
    B.5.3.1Street Address1000 de la Gauchetière West, Suite 1200
    B.5.3.2Town/ cityMontreal, Quebec
    B.5.3.3Post codeH3B 4W5
    B.5.3.4CountryCanada
    B.5.4Telephone number0015149403614
    B.5.6E-maileric.soliman@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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameIPN60130 10 mg capsules
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Capsule
    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.3.9.2Current sponsor codeIPN60130
    D.3.9.3Other descriptive name(R)-tetrahydrofuran-3-yl 4-(6-(5-(4-ethoxy-1-isopropylpiperidin-4- yl)pyridine-2yl)pyrrolo[1,2-b]pyridazin-4-yl)piperazine-1-carboxylate sesquisuccinate
    D.3.9.4EV Substance CodeSUB206522
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameIPN60130 50 mg capsules
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Capsule
    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.3.9.2Current sponsor codeIPN60130
    D.3.9.3Other descriptive name(R)-tetrahydrofuran-3-yl 4-(6-(5-(4-ethoxy-1-isopropylpiperidin-4- yl)pyridine-2yl)pyrrolo[1,2-b]pyridazin-4-yl)piperazine-1-carboxylate sesquisuccinate
    D.3.9.4EV Substance CodeSUB206522
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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
    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)
    fibrodisplasia ossificante progressiva
    E.1.1.1Medical condition in easily understood language
    fibrodysplasia ossificans progressiva
    fibrodisplasia ossificante progressiva
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    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
    • Evaluate the efficacy of IPN60130 monotherapy compared with
    placebo recipients in inhibiting new heterotopic ossification (HO) volume
    in adult and paediatric participants with FOP as assessed by low-dose
    whole body computed tomography (WBCT) (excluding the head)
    • Evaluate the safety of IPN60130 in adult and paediatric participants
    with FOP
    • Valutare l’efficacia di IPN60130 in monoterapia rispetto al placebo nell’inibizione del volume di nuova OE in partecipanti adulti e pediatrici con FOP valutata con WBCT a basso dosaggio, esclusa la testa

    • Valutare la sicurezza di IPN60130 in partecipanti adulti e pediatrici con FOP
    E.2.2Secondary objectives of the trial
    • Change in HO volume of new HO lesions over time by WBCT at M12.
    • Number of new HO lesions by WBCT at M12.
    • Rate and number of flare-up days at M12.
    • The number of body regions with new HO at M12.
    • To evaluate the effect of IPN60130 on pain intensity over time at M12.
    • Proportion of participants with new HO by WBCT
    • Change in HO volume over time as detected by WBCT.
    Pharmacokinetic
    • To evaluate the pharmacokinetics of IPN60130.
    Exposure-Response
    • To evaluate the exposure-response relationship, if feasible.
    • Variazione del volume di nuove lesioni OE nel tempo rilevata con WBCT al Mese 12
    • Numero di nuove lesioni OE rilevate con WBCT al Mese 12
    • Tasso e numero di giorni di flare-up al Mese 12
    • Numero di sedi corporee con nuova OE al Mese 12
    • Valutare l’effetto di IPN60130 sull’intensità del dolore nel tempo al Mese 12
    • Proporzione di partecipanti con nuove OE rilevate con WBCT
    • Variazione del volume di OE nel tempo rilevate con WBCT
    Farmacocinetica:
    • Valutare la farmacocinetica di IPN60130
    Esposizione-risposta:
    • Valutare il rapporto esposizione-risposta, ove fattibile
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives

    Other types of substudies
    Specify title, date and version of each substudy with relative objectives: Fluorine-18-labelled natrium fluoride ([18F]NaF) Positron Emission Tomography-Computed Tomography PET-CT Substudy:

    Objectives:
    • Change from baseline in HO lesion activity as detected by [18F]NaF PET-CT
    • Change from baseline in number of HO lesion by [18F]NaF PET-CT
    • Correlation of HO lesion activity by [18F]NaF PET-CT in new HO lesions by WBCT

    Inclusion criterion (Age):
    • Participants must be at least 15 years of age at the time of signing the informed participant/parent consent for the main study and, for participants who are minors, age-appropriate assent.

    Altre tipologie di sottostudi
    specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Sottostudio di tomografia computerizzata ad emissione di positroni PET-TAC con sodio fluoruro legato a fluoro 18 ([18F]NaF):

    Obiettivi:
    Variazione dal basale nell’attività della lesione HO rilevata mediante [18F]NaF PET-TAC
    Variazione dal basale nel numero di lesioni HO mediante [18F]NaF PET-CT
    Correlazione dell’attività della lesione HO mediante [18F]NaF PET-CT in nuove lesioni HO mediante TAC-WB

    Criterio di inclusione (età):
    I partecipanti devono avere almeno 15 anni di età al momento della firma del modulo di consenso informato per il partecipante/genitore per lo studio principale e, per i partecipanti che sono minorenni, dell’assenso appropriato per l’età.
    E.3Principal inclusion criteria
    Age – Main Study
    1. at least 5 years of age, to be confirmed (entry for younger paediatric participants <15 years of age will only be once safety in adult and older paediatric participants =15 years of age has been
    established) at the time of signing the informed participant/parent consent and, for participants who are minors, age-appropriate assent.
    Age – [18F]NaF PET-CT Imaging Substudy
    2. least 15 years of age at the time of signing the informed participant/parent consent for the main study and, for participants who are minors, age-appropriate assent.

    Type of Participant and Disease Characteristics.:
    3. Participants must be clinically diagnosed with FOP, with the R206H ACVR1 mutation or other FOP variants associated with progressive HO.
    4. Participants must have at least one flare-up in the preceding year of the screening visit.
    5. Participants who have participated in a prior clinical study using another investigational product for the treatment of FOP may be enrolled after a washout of at least 5 half-lives of the other investigational
    product. Participants with prior treatment such as, but not limited to, imatinib, isotretinoin, or palovarotene may be enrolled 30 days after discontinuation or after washout of at least 5 half-lives, whichever is longer.
    6. Participants must be able to perform pulmonary function tests adequately and reliably.
    7. Participants must be able to have an adequate echocardiography assessment at screening for evaluation of left ventricular structure and
    function as defined by the protocol.
    8. Participants must be accessible for treatment and follow-up and be able to undergo all study procedures. Participants living at distant locations from the investigational site must be able and willing to travel
    to a site for the initial and all on-site follow-up visits. Participants must be able to undergo low-dose WBCT (excluding head) without sedation.

    Weight
    9. Body weight =10 kg.

    Sex
    10.Male and/or female participants:
    Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
    a. Male participants:
    Male participants of child bearing potential must agree to remain
    abstinent from heterosexual sex during treatment and for 1 month after
    treatment or, if sexually active, to use two effective methods of birth
    control, one of which must be highly effective during and for 1 month after treatment. The agreement to remain abstinent or use two effective
    methods (one of which must be highly effective) of birth control will be
    clearly defined in the informed consent; the participant or legally
    authorized representatives (e.g. parents, caregivers, or legal guardians)
    must sign this specific section.
    b. Female participants:
    Females of childbearing potential (defined in Appendix 10.5.1) must
    have a negative blood or urine pregnancy test (with sensitivity of at
    least 50 mIU/mL) prior to administration of study drug. FOCBP
    participants must agree to remain abstinent from heterosexual sex
    during treatment and for 1 month after treatment or, if sexually active,
    to use two effective methods of birth control, one of which must be
    highly effective during and for 1 month after treatment. Additionally,
    sexually active FOCBP participants in a heterosexual relationship must
    already be using two effective methods of birth control (one of which
    must be highly effective) 1 month before treatment is to start.
    Specific risks of study drug use during pregnancy as well as the
    agreement to remain abstinent or use two effective methods of birth
    control (one of which must be highly effective) will be clearly defined in
    the informed consent; the participant or legally authorized
    representatives (e.g. parents, caregivers, or legal guardians) must sign
    this specific section.

    Insufficient space, please refer to Protocol
    Età - Studio principale
    1. I partecipanti devono avere almeno 5 anni di età (l’ingresso per i partecipanti pediatrici più giovani con <15 anni di età avverrà solo quando sarà stabilita la sicurezza nei partecipanti adulti e pediatrici più grandi di età =15 anni) da confermare al momento della firma del modulo di consenso informato per il partecipante/genitore e, per i partecipanti che sono minorenni, dell’assenso appropriato per l’età.
    Età – Sottostudio di imaging con [18F]NaF PET-CT
    2. I partecipanti devono avere almeno 15 anni di età al momento della firma del modulo di consenso informato per il partecipante/genitore per lo studio principale e, per i partecipanti che sono minorenni, dell’assenso appropriato per l’età.
    Tipo di partecipante e caratteristiche della malattia
    3. I partecipanti devono avere una diagnosi clinica di FOP, con mutazione R206H ACVR1 o altre varianti FOP associate a HO progressiva.
    4. I partecipanti devono avere avuto almeno una riacutizzazione nell’anno precedente alla visita di screening.
    5. I partecipanti che hanno preso parte a uno studio clinico precedente usando un altro medicinale sperimentale per il trattamento della FOP possono essere arruolati dopo un periodo di washout di almeno 5 emivite dell’altro medicinale sperimentale. I partecipanti con precedente trattamento quale, a titolo esemplificativo, imatinib, isotretinoina o palovarotene, possono essere arruolati 30 giorni dopo l’interruzione o dopo il washout di almeno 5 emivite, in base a quale sia il periodo più lungo.
    6. I partecipanti devono essere in grado di eseguire gli esami di funzionalità polmonare in modo adeguato e affidabile.
    7. I partecipanti devono essere in grado di ricevere una valutazione ecocardiografica adeguata allo screening per la valutazione della struttura e della funzione ventricolare sinistra come definito nel protocollo.
    8. I partecipanti devono essere raggiungibili per il trattamento e il follow-up ed essere in grado di sottoporsi a tutte le procedure dello studio. I partecipanti che vivono in luoghi distanti dal centro della sperimentazione devono essere in grado e avere la volontà di recarsi al centro per la visita iniziale e tutte le visite di follow-up presso il centro. I partecipanti devono essere in grado di sottoporsi a TAC-WB (esclusa la testa) a basso dosaggio senza sedazione.
    9. Peso corporeo =10 kg.
    10. Partecipanti di sesso maschile e/o femminile:
    L’uso dei contraccettivi da parte degli uomini o delle donne deve essere coerente con le normative locali riguardanti i metodi contraccettivi per i partecipanti a studi clinici.
    a. Partecipanti di sesso maschile:
    I partecipanti di sesso maschile potenzialmente fertili devono acconsentire ad astenersi da rapporti sessuali eterosessuali durante il trattamento e per 1 mese dopo il trattamento oppure, se sessualmente attivi, devono usare due metodi contraccettivi efficaci, uno dei quali deve essere altamente efficace, durante il trattamento e per 1 mese dopo il trattamento. Il consenso a osservare l’astinenza o usare due metodi contraccettivi efficaci (uno dei quali deve essere altamente efficace) sarà chiaramente definito nel consenso informato; il partecipante o i rappresentanti legalmente autorizzati (ad es. i genitori, i caregiver o i tutori legali) devono firmare tale sezione specifica.
    b. Partecipanti di sesso femminile:
    Le donne in età fertile (FOCBP) (come definito nell’Appendice 10.5.1) devono avere un test di gravidanza sierico o urinario negativo (con sensibilità di almeno 50 mUI/ml) prima della somministrazione del farmaco in studio. Le partecipanti FOCBP devono acconsentire ad astenersi dal rapporti sessuali eterosessuali durante il trattamento e per 1 mese dopo il trattamento oppure ......

    Spazio insufficiente, si prega di fare riferimento al Protocollo.
    E.4Principal exclusion criteria
    Medical Conditions
    1. Participants with complete heart block and left bundle branch block on
    screening electrocardiogram.
    2. Participants with screening echocardiograph showing septal or left
    ventricular free wall thickness >12 mm for adult participants or a zscore >3 compared with population norms for children and adolescent

    participants.
    3. Participants with severe mitral or tricuspid regurgitation on

    echocardiograph at
    screening.
    4. Participants with significant underlying lung disease requiring

    supplementary oxygen or forced vital capacity <35% of predicted at

    screening.
    5. Participants with uncontrolled cardiovascular, hepatic, pulmonary,

    gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic,

    psychiatric, or other significant disease as judged by the investigator.

    6. Participants with severe hepatic
    impairment.
    Prior/Concomitant Therapy
    7. Concomitant medications that are strong inhibitors (including
    grapefruit juice) or inducers (including St John's Wort) of cytochrome
    P450 (CYP) 3A4 activity and strong inhibitors or inducers of CYP2C19
    activity; or kinase inhibitors such as imatinib.
    8. Prior use in the past year and concomitant use of bisphosphonates for
    participants in the PET-CT substudy.
    Prior/Concurrent Clinical Study Experience
    9. Concurrent participation in another interventional clinical study, or a
    noninterventional study with radiographic measures or invasive
    procedures (e.g. collection of blood or tissue samples).
    Other Exclusions
    1. Amylase or lipase >2× the upper limit of normal (ULN) or with a
    history of chronic pancreatitis.
    2. Elevated aspartate aminotransferase (AST) or alanine
    aminotransferase (ALT) >2.5×ULN.
    3. Participants with hematologic abnormalities:
    • Hgb<10g/dL
    • Platelets<75,000/mm3
    • WBC<2000/mm3
    • Participants with coagulation test (prothrombin time [PT]/
    international normalised ratio [INR], and activated partial
    thromboplastin time [aPTT]) measurements outside of the normal range
    at screening.
    4. Female participants who are breastfeeding.
    5. 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
    Individuals with disqualifying laboratory abnormalities may be
    rescreened once within the screening window. Rescreening may be
    repeated more than once if the results are atypical for the participant
    based on prior results from preceding year.
    I partecipanti sono esclusi dallo studio se si applica uno qualsiasi dei seguenti criteri:

    Condizioni mediche
    1. Partecipanti con blocco cardiaco completo e con blocco di branca sinistra all’elettrocardiogramma di screening.
    2. Partecipanti con ecocardiogramma di screening che mostra spessore della parete libera ventricolare sinistra o del setto >12 mm per i partecipanti adulti o uno z-score >3 rispetto alla norma della popolazione per i partecipanti pediatrici (bambini e adolescenti).
    3. Partecipanti con grave rigurgito mitrale o tricuspide all’ecocardiogramma di screening.
    4. Partecipanti con malattia polmonare di base importante che richiede supplemento di ossigeno o con capacità vitale forzata <35% del previsto allo screening.
    5. Partecipanti che, a parere dello sperimentatore, hanno una malattia non controllata cardiovascolare, epatica, polmonare, gastrointestinale, endocrina, metabolica, oftalmica, immunologica, psichiatrica o di altro tipo.
    6. Partecipanti con grave compromissione epatica.

    Terapia precedente/concomitante
    7. Medicinali concomitanti che sono forti inibitori (compreso il succo di pompelmo) o induttori (compresa l’erba di San Giovanni) dell’attività del citocromo P450 (CYP) 3A4 e forti inibitori o induttori dell’attività del CYP2C19; o inibitori della chinasi come imatinib.
    8. Precedente uso nell’anno passato e uso concomitante di bisfosfonati per i partecipanti al sottostudio PET-TAC.
    Precedente/concomitante esperienza in uno studio clinico
    9. Simultanea partecipazione ad altro studio clinico interventistico, o ad uno studio non-interventistico con misurazioni radiografiche o procedure invasive (per es. raccolta di sangue o di campioni tissutali).

    Altre esclusioni
    1. Amilasi o lipasi >2x il limite superiore della norma (ULN) o anamnesi di pancreatite cronica.
    2. Aspartato aminotransferasi (AST) o alanina aminotransferasi (ALT) elevata >2,5xULN.
    3. Partecipanti con anomalie ematologiche:
    Hgb <10g/dl
    Piastrine <75.000/mm3
    WBC <2000/mm3
    Partecipanti con esiti del test della coagulazione (tempo di protrombina [PT]/rapporto internazionale normalizzato [INR], e tempo di tromboplastina parziale attivato [aPTT]) al di fuori dell’intervallo normale allo screening.
    4. Partecipanti di sesso femminile che allattano con latte materno.
    5. Qualsiasi motivo che, a parere dello sperimentatore, comporterebbe l’incapacità del partecipante e/o della famiglia di rispettare il protocollo. Individui con anomalie di laboratorio che sono squalificanti potranno essere sottoposti a nuovo screening quando tali valori saranno rientrati nella finestra dello screening. La ripetizione dello screening può essere fatta più di una volta se i risultati sono atipici per il partecipante in base ai risultati precedenti dell’anno prima.
    E.5 End points
    E.5.1Primary end point(s)
    • The annualized change from baseline in HO volume as assessed by
    low-dose WBCT (excluding the head) in treated participants receiving
    IPN60130 through M12 compared with placebo
    • Adverse events / serious adverse events (AEs/SAE), cardiac outcomes
    (electrocardiogram (ECG), echocardiograms, cardiac biomarkers), vital
    signs, physical examinations, body weight and height, laboratory
    parameters, serum or urine pregnancy tests for females of childbearing
    potential (FOCBP), concomitant medications
    Variazione annualizzata dal basale nel volume di HO valutata mediante TAC-WB (esclusa la testa) a basso dosaggio nei pazienti trattati che hanno ricevuto IPN60130 fino a M12 rispetto al placebo
    Eventi Avversi/Eventi Avversi Gravi (AE/SAE), esiti cardiaci (elettrocardiogramma (ECG), ecocardiogramma, biomarcatori cardiaci), parametri vitali, esame obiettivo, peso corporeo e altezza, parametri di laboratorio, test di gravidanza sierico o urinario per le donne in età fertile (FOCBP), medicinali concomitanti
    E.5.1.1Timepoint(s) of evaluation of this end point
    • WBCT: Pt A: D1, M6, M12 ; Pt B: M18, M24, ET
    • AEs/SAEs and Concomitant medications: at screening and at every
    participant contact
    • ECG and echocardiograms: Pt A: Screening, M1, M3, M6, M12 ; Pt B:
    M13, M15, M18, M24, ET
    • Cardiac biomarkers (inc. Troponin I (HS) & NT-proBNP): Pt A
    :Screening, D1, M1, M3, M6, M12 ; Pt B: M13, M15, M18, M24, ET
    • Vital signs / Physical examination: Pt A: Screening, D1, M3, M6, M12 ;
    Pt B: M13, M15, M18, M24
    • Body weight and height: Pt A: Screening, D1, M6, M12 ; Pt B: M18,
    M24, ET
    • Laboratory parameters: Pt A: Screening, D1, M1, M3, M6, M12 ; Pt B:
    M13, M15, M18, M24, ET
    • Serum / urine pregnancy tests: every month
    Where
    Pt = Part
    D = Day
    M = Month
    ET = early termination
    EoS = end of study
    TAC-WB: Pt A: G1, M6, M12 ; Pt B: M18, M24, ET
    AE/SAE e medicinali concomitanti: allo screening e ad ogni contatto con il partecipante
    ECG e ecocardiogramma: Pt A: Screening, M1, M3, M6, M12 ; Pt B: M13, M15, M18, M24, ET
    Biomarcatori cardiaci (inc. Troponina I (HS) e NT-proBNP): Pt A
    Screening, G1, M1, M3, M6, M12; Pt B: M13, M15, M18, M24, ET
    Parametri vitali / Esame obiettivo: Pt A: Screening, G1, M3, M6, M12; Pt B: M13, M15, M18, M24
    Peso corporeo e altezza: Pt A: Screening, G1, M6, M12 ; Pt B: M18, M24, ET
    Parametri di laboratorio: Pt A: Screening, G1, M1, M3, M6, M12; Pt B: M13, M15, M18, M24, ET
    Test di gravidanza sierico / urinario: ogni mese

    Dove
    Pt = Parte
    G = Giorno
    M = Mese
    ET = Interruzione anticipata
    EoS = Termine dello studio
    E.5.2Secondary end point(s)
    • Change from baseline in HO volume of new HO lesions as detected by
    WBCT in participants receiving IPN60130 compared with placebo
    recipient at M12.
    • Change from baseline in number of HO lesions by WBCT in participants
    receiving IPN60130 compared with placebo recipients at M12.
    • Flare-up rate and number of flare-up days in participants receiving
    INP60130 compared with placebo at M12
    • The number of body regions with new HO in participants treated with
    IPN60130 compared with placebo recipients at M12
    • Change from baseline in pain intensity over time assessed using the
    NRS in participants =13 years of age and the Wong Baker FPS in
    participants <13 years of age for participants receiving IPN60130
    compared with placebo recipients at M12
    • The proportion of participants with any new HO in participants
    receiving IPN60130 compared with placebo recipients through M24.
    • Change from baseline in HO volume as detected by WBCT in
    participants receiving IPN60130 compared with placebo recipients and
    with participants receiving the standard of care in the NHS through M24.
    Pharmacokinetic
    • Pharmacokinetic parameters by population PK modelling using all
    sparse samples collected during the study
    Exposure-Response
    • Exposure-response analysis by modelling using relevant efficacy and
    safety parameters
    Variazione dal basale nel volume di HO delle nuove lesioni HO rilevate mediante TAC-WB in partecipanti che ricevono IPN60130 rispetto a quelli che ricevono il placebo al M12.
    Variazione dal basale nel numero di lesioni HO rilevate mediante TAC-WB in partecipanti che ricevono IPN60130 rispetto a quelli che ricevono il placebo al M12.
    Tasso di riacutizzazione e numero di giorni di riacutizzazione in partecipanti che ricevono INP60130 rispetto a quelli che ricevono il placebo al M12
    Il numero di regioni corporee con nuove HO in partecipanti trattati con IPN60130 rispetto a quelli trattati con placebo al M12
    Variazione dal basale nell’intensità del dolore nel periodo di valutazione usando l’NRS in partecipanti con età =13 anni e il Wong Baker FPS in partecipanti con età <13 anni per i partecipanti che ricevono IPN60130 rispetto a quelli che ricevono il placebo al M12
    Proporzione di partecipanti con qualsiasi nuova HO in partecipanti che ricevono IPN60130 rispetto a quelli che ricevono placebo fino al M24.
    Variazione dal basale nel volume di HO rilevato mediante TAC-WB in partecipanti che ricevono IPN60130 rispetto a quelli che ricevono il placebo e a quelli che ricevono lo standard di cura nel Sistema Sanitario Nazionale fino al M24.
    Farmacocinetica
    Parametri farmacocinetici per modellazione PK della popolazione usando tutti i campioni sparsi raccolti durante lo studio
    Esposizione-Risposta
    Analisi esposizione-risposta mediante modellazione usando parametri attinenti di efficacia e sicurezza
    E.5.2.1Timepoint(s) of evaluation of this end point
    As per E.5.1.1 and additionally;
    NRS and FPS: Pt A: D1, M1 - M12 ; Pt B: M13, M15, M18, M24, ET, EoS
    Come da E.5.1.1 e in aggiunta;
    NRS e FPS: Pt A: G1, M1 - M12; Pt B: M13, M15, M18, M24, ET, EoS
    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 No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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) 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 Yes
    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.8.4.1Number 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 EEA10
    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 Information not present in EudraCT
    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
    China
    France
    Germany
    Italy
    Japan
    Korea, Republic of
    Mexico
    Netherlands
    Russian Federation
    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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days19
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months7
    E.8.9.2In all countries concerned by the trial days19
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    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: 18
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 23
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 9
    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 35
    F.4.2.2In the whole clinical trial 90
    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)
    None
    Nessuno.
    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 Decision2021-06-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-04-19
    P. End of Trial
    P.End of Trial StatusOngoing
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