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    Summary
    EudraCT Number:2018-004530-14
    Sponsor's Protocol Code Number:1199-0337
    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:2021-06-15
    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 number2018-004530-14
    A.3Full title of the trial
    A double blind, randomised, placebo-controlled trial to evaluate the dose-exposure and safety of nintedanib per os on top of standard of care for 24 weeks, followed by open label treatment with nintedanib of variable duration, in children and adolescents (6 to 17 year-old) with clinically significant fibrosing Interstitial Lung Disease.
    Studio clinico in doppio cieco, randomizzato e controllato versus placebo volto a valutare dose/esposizione e sicurezza di nintedanib somministrato per via orale per 24 settimane in aggiunta alla terapia standard, seguito da un trattamento in aperto con nintedanib di durata variabile, in bambini e adolescenti (da 6 a 17 anni) affetti da interstiziopatia polmonare (ILD) fibrosante clinicamente significativa.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to find out how nintedanib is taken up in the body and how well it is tolerated in children and adolescents with Interstitial Lung Disease (ILD).
    Studio per scoprire come nintedanib viene assorbito nel corpo e quanto è tollerato nei bambini e negli adolescenti affetti da interstiziopatia polmonare (ILD).
    A.3.2Name or abbreviated title of the trial where available
    -
    -
    A.4.1Sponsor's protocol code number1199-0337
    A.5.4Other Identifiers
    Name:-Number:-
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/150/2019
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBOEHRINGER-INGELHEIM ITALIA S.P.A.
    B.1.3.4CountryItaly
    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 supportBOEHRINGER-INGELHEIM ITALIA S.P.A.
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBoehringer Ingelheim
    B.5.2Functional name of contact pointQRPE PSC CT Information Disclosure
    B.5.3 Address:
    B.5.3.1Street AddressBinger Strasse 173
    B.5.3.2Town/ cityIngelheim am Rhein
    B.5.3.3Post code55216
    B.5.3.4CountryGermany
    B.5.4Telephone number00498002430127
    B.5.5Fax number00498008217119
    B.5.6E-mailclintriage.rdg@boehringeringelheim.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 Yes
    D.2.1.1.1Trade name Ofev
    D.2.1.1.2Name of the Marketing Authorisation holderBoehringer Ingelheim International GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameNintedanib 150mg capsules
    D.3.2Product code [Nintedanib]
    D.3.4Pharmaceutical form Capsule, soft
    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 INNNINTEDANIB
    D.3.9.1CAS number 656247-17-5
    D.3.9.2Current sponsor codeNintedanib
    D.3.9.4EV Substance CodeSUB120728
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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 Yes
    D.2.1.1.1Trade name Ofev
    D.2.1.1.2Name of the Marketing Authorisation holderBoehringer Ingelheim Internactional GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameNintedanib 100 mg capsules
    D.3.2Product code [Nintedanib]
    D.3.4Pharmaceutical form Capsule, soft
    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 INNNINTEDANIB
    D.3.9.2Current sponsor codeNINTEDANIB
    D.3.9.4EV Substance CodeSUB120728
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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: 3
    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 nameNintedanib 25 mg capsules
    D.3.2Product code [Nintedanib]
    D.3.4Pharmaceutical form Capsule, soft
    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 INNNINTEDANIB
    D.3.9.2Current sponsor codeNINTEDANIB
    D.3.9.4EV Substance CodeSUB120728
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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, soft
    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 placeboCapsule, soft
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule, soft
    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
    Interstitial Lung Disease
    interstiziopatia polmonare (ILD) fibrosante
    E.1.1.1Medical condition in easily understood language
    Interstitial Lung Disease
    interstiziopatia polmonare (ILD) fibrosante
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level SOC
    E.1.2Classification code 10038738
    E.1.2Term Respiratory, thoracic and mediastinal disorders
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The main objective of the study is to evaluate dose-exposure and safety
    of nintedanib in children and adolescents with fibrosing ILD.
    L’obiettivo principale dello studio è valutare dose/esposizione e sicurezza di nintedanib in bambini e adolescenti affetti da interstiziopatia polmonare fibrosante.
    E.2.2Secondary objectives of the trial
    N.A.
    N.A.
    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: HRCT substudy:
    In selected sites in the United States only, patients will have the option
    to participate in a longitudinal HRCT substudy.
    Details of the planned HRCT analyses and endpoints will be described in
    a specific Statistical Analysis Plan (SAP) for the substudy and are
    considered exploratory.

    Altre tipologie di sottostudi
    specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Sottostudio HRCT che non si tiene in ITALIA
    E.3Principal inclusion criteria
    -Children and adolescents 6 to 17 years old at Visit 2.
    -Signed and dated written informed consent and assent, where
    applicable, in accordance with ICH-GCP and local legislation prior to
    admission to the trial.
    -Male or female patients. Female of childbearing potential (WOCBP)
    must confirm that sexual abstinence is standard practice and will be
    continued until 3 months after last drug intake, or be ready and able to
    use a highly effective method of birth control per ICH M3 (R2) that
    results in a low failure rate of less than 1% per year when used
    consistently and correctly, in combination with one barrier method, from
    28 days prior to initiation of study treatment, during treatment and until
    3 months after last drug intake. Sexual abstinence is defined as
    abstinence from any sexual act that may result in pregnancy.
    -Patients with evidence of fibrosing ILD on HRCT within 12 months of
    Visit 1 as assessed by the investigator and confirmed by central review.
    -Patients with FVC % predicted >=25% at Visit 2.
    -Patients with clinically significant disease at Visit 2, as assessed by the
    investigator based on any of the following: Fan score >=3, or documented
    evidence of clinical progression over time based on either
    a 5-10% relative decline in FVC% predicted accompanied by worsening
    symptoms, or
    a >=10% relative decline in FVC % predicted, or
    increased fibrosis on HRCT, or
    other measures of clinical worsening attributed to progressive lung
    disease (e.g. increased oxygen requirement, decreased diffusion
    capacity).
    1. Bambini e adolescenti dai 6 ai 17 anni di età alla Visita 2.
    2. Consenso informato scritto firmato e datato e assenso, ove applicabile, prima dell’inclusione nella sperimentazione, in conformità alle norme ICH-GCP e alla normativa locale.
    3. Pazienti di ambo i sessi. Per la donna potenzialmente fertile andrà confermata l’astinenza sessuale come pratica che verrà osservata fino a 3 mesi dopo l’ultima assunzione del farmaco, oppure andrà confermato che è disposta e in grado di utilizzare un metodo contraccettivo altamente efficace secondo le linee guida ICH M3 (R2), con una percentuale di insuccesso inferiore all’1% all’anno se usato in modo coerente e corretto, in combinazione con un metodo barriera da 28 giorni prima dell’inizio del trattamento in studio, durante tutto il trattamento e fino a 3 mesi dopo l’ultima assunzione del farmaco. L’astinenza sessuale è definita come l’astinenza da qualsiasi rapporto sessuale che potrebbe portare ad una gravidanza. Nel foglio informativo per i genitori è riportato un elenco dei metodi contraccettivi che soddisfano i suddetti criteri.
    4. Pazienti con evidenza di ILD fibrosante all’HRCT entro 12 mesi dalla Visita 1, valutata dallo sperimentatore e confermata da una revisione centralizzata.
    5. Pazienti con FVC prevista >= 25% alla Visita 2.
    Nota: i valori normali previsti saranno calcolati secondo la GLI (Global Lung Initiative).
    6. Pazienti con malattia clinicamente significativa alla Visita 2, valutata dallo sperimentatore in base a uno dei seguenti criteri:
    - Fan score >=3 oppure
    - Evidenza documentata di progressione clinica nel tempo basata su:
    a un declino relativo del 5-10% della FVC prevista, accompagnato da un peggioramento dei sintomi; oppure
    b un declino relativo >=10% della FVC prevista; o
    c un aumento della fibrosi all’HRCT; oppure
    d altre misure di peggioramento clinico attribuite alla malattia polmonare progressiva (ad es. aumento del fabbisogno di ossigeno, diminuzione della capacità di diffusione).
    E.4Principal exclusion criteria
    AST and/or ALT and/or bilirubin >1.5 x ULN, and/or creatinine clearance
    <30 mL/min (Schwartz formula), and/or underlying chronic liver
    disease (Child Pugh A, B or C hepatic impairment) at Visit 1; previous
    treatment with nintedanib, other investigational therapy received within
    1 month or 5 half-lives (whichever is shorter but >=1 week) prior to Visit
    2; significant pulmonary arterial hypertension, any cardiovascular
    disease excluded by protocol, history of thrombotic event within 12
    months of Visit 1, other disease that may interfere with testing
    procedures or trial participation, or may put the patient at risk; bleeding
    risk; life expectancy for any concomitant disease other than ILD <2.5
    years (investigator assessment); any diagnosed growth disorder or any
    genetic disorder associated with short stature and/or treatment with
    growth hormone therapy within 6 months before Visit 2; <13.5 kg of
    weight at Visit 1.
    1. AST e/o ALT >1,5 x ULN alla Visita 1.
    2. Bilirubina >1,5 x ULN alla Visita 1.
    3. Clearance della creatinina calcolata mediante la formula di Schwartz <30 ml/min alla Visita 1.
    4. Pazienti con epatopatia cronica (di grado A, B o C secondo la classificazione Child Pugh) alla Visita 1.
    5. Trattamento precedente con nintedanib.
    6. Trattamento con un’altra terapia sperimentale entro 1 mese o 5 emivite (a seconda di quale periodo è più breve ma >=1 settimana) prima della Visita 2.
    7. Ipertensione arteriosa polmonare significativa, definita da uno dei seguenti criteri:
    a. Precedente evidenza clinica o ecocardiografica di insufficienza cardiaca destra significativa
    b. Storia di cateterizzazione cardiaca destra che mostra un indice cardiaco <=2 l/min/m²
    c. Ipertensione arteriosa polmonare che richiede la terapia parenterale con epoprostenolo/treprostinil
    8. Altre anomalie polmonari clinicamente significative secondo il parere dello sperimentatore.
    9. Una qualsiasi delle seguenti malattie cardiovascolari:
    a. Ipertensione grave, non controllata durante dalla terapia medica, entro 6 mesi dalla Visita 1 (vedi sinossi).
    b. Infarto miocardico entro 6 mesi dalla Visita 1
    c. Angina instabile entro 6 mesi dalla Visita 1
    10. Rischio di sanguinamento associato a una delle seguenti condizioni:
    a. Note predisposizione genetica al sanguinamento
    b. Pazienti che richiedono:
    i. fibrinolisi, terapia anticoagulante a dosaggio pieno (ad es. antagonisti della vitamina K, inibitori diretti della trombina, eparina, irudina)
    ii. Terapia antipiastrinica ad alto dosaggio
    c. Storia di evento emorragico a carico del sistema nervoso centrale (SNC) entro 12 mesi dalla Visita 1
    d. Una qualsiasi delle seguenti condizioni entro 3 mesi dalla Visita 1:
    i. Emottisi o ematuria
    ii. Sanguinamento gastrointestinale (GI) attivo o ulcere GI
    iii. Lesioni o interventi chirurgici importanti (secondo il parere dello sperimentatore)
    e. Uno qualsiasi dei seguenti parametri di coagulazione alla Visita 1:
    i. INR (International Normalized Ratio) >2
    ii. PT (Prothrombin Time) >1,5 x ULN
    iii. aPTT (activated Partial Thromboplastin Time) >1,5 x ULN
    11. Storia di evento trombotico (inclusi ictus e attacco ischemico transitorio) entro 12 mesi dalla Visita 1.
    12. Nota ipersensibilità al farmaco sperimentale o ai suoi componenti (ad es. alla lecitina di soia).
    13. Pazienti con documentata allergia alle arachidi o alla soia
    14. Altre patologie che potrebbero interferire con le procedure di test o che, a giudizio dello sperimentatore, potrebbero interferire con la partecipazione alla sperimentazione o mettere a rischio il paziente in caso di partecipazione a questo studio.
    15. Aspettativa di vita per qualsiasi malattia concomitante diversa dalla ILD <2,5 anni (secondo la valutazione dello sperimentatore).
    16. Pazienti di sesso femminile in gravidanza, allattamento o che prevedono di avviare una gravidanza durante la sperimentazione.
    17. Pazienti che non sono in grado o disposti ad aderire alle procedure della sperimentazione, compresa l’assunzione del farmaco in studio.
    18. Pazienti con disturbi della crescita diagnosticati quali la carenza di ormone della crescita o qualsiasi disturbo genetico associato a bassa statura (ad es. sindrome di Turner, sindrome di Noonan, sindrome di Russell-Silver) e/o trattamento a base dell’ormone della crescita entro 6 mesi prima della Visita 2. Possono essere inclusi i pazienti con bassa statura che, secondo il parere dello sperimentatore, è dovuta alla terapia a base di glucocorticoidi.
    19. Pazienti di peso <13,5 kg alla Visita 1 (stessa soglia sia per i pazienti di sesso maschile che per quelli di sesso femminile).
    E.5 End points
    E.5.1Primary end point(s)
    1) PK: AUCt,ss based on sampling at steady state
    2) N (%) of patients with treatment-emergent adverse events
    1) PK: AUCt,ss basata sul campionamento allo stato stazionario (alla settimana 2 e alla settimana 26);
    2) Numero (%) di pazienti con eventi avversi emergenti dal trattamento alla settimana 24.
    E.5.1.1Timepoint(s) of evaluation of this end point
    1) weeks 2 and 26
    2) week 24
    1) alla settimana 2 e alla settimana 26
    2) alla settimana 24
    E.5.2Secondary end point(s)
    1) N (%) of patients with treatment-emergent pathological findings of
    epiphyseal growth plate on imaging at week 24, and week 52*;
    2) N (%) of patients with treatment-emergent pathological findings on
    dental examination or imaging at week 24, and week 52*;
    3) N (%) of patients with treatment-emergent adverse events over the
    whole trial;
    4) Change in height, sitting height, leg length from baseline at week 24,
    week 52*, week 76*, and week 100*.
    5) Change in Forced Vital Capacity (FVC) % predicted from baseline at
    week 24, and week 52*;
    6) Absolute change from baseline in Pediatric Quality of Life
    Questionnaire™ (PedsQL™) at week 24, and week 52*;
    7) Change in oxygen saturation (SpO2) on room air at rest from baseline
    at week 24, and week 52*;
    8) Change in 6-min walk distance from baseline at week 24, and week
    52*;
    9) Patient acceptability based on the size of capsules at week 24;
    10) Patient acceptability based on the number of capsules at week 24;
    11) Time to first respiratory-related hospitalization over the whole trial;
    12) Time to first acute Interstitial Lung Disease (ILD) exacerbation or
    death over the whole trial;
    13) Time to death over the whole trial;
    *52 weeks, 76 weeks, 100 weeks time points will not be available for all
    patients
    1) Numero (%) di pazienti con findings patologici, emergenti dal trattamento, della piastra di crescita epifisaria rilevati tramite imaging alla settimana 24 e alla settimana 52*;
    2) Numero (%) di pazienti con findings patologici, emergenti dal trattamento, rilevati tramite esame odontoiatrico o imaging alla settimana 24 e alla settimana 52*;
    3) Numero (%) di pazienti con eventi avversi emergenti dal trattamento nel corso dell’intera sperimentazione;
    4) Variazione dell’altezza, dell’altezza in posizione seduta e della lunghezza della gamba dal basale alle settimane 24, 52*, 76* e 100*.
    5) Variazione della Capacità Vitale Forzata (FVC) % prevista dal basale alla settimana 24 e alla settimana 52*;
    6) Variazione assoluta nel questionario Pediatric Quality of Life™ (PedsQL™) dal basale alla settimana 24 e alla settimana 52*;
    7) Variazione della saturazione di ossigeno (SpO2) in aria ambiente a riposo dal basale alla settimana 24 e alla settimana 52*;
    8) Variazione della distanza percorsa in 6 minuti dal basale alla settimana 24 e alla settimana 52*;
    9) Accettabilità del paziente in base alle dimensioni delle capsule alla settimana 24;
    10) Accettabilità del paziente in base al numero di capsule alla settimana 24;
    11) Tempo al primo ricovero per motivi respiratori nel corso dell’intera sperimentazione;
    12) Tempo alla prima esacerbazione acuta dell’interstiziopatia polmonare (ILD) o al decesso nel corso dell’intera sperimentazione;
    13) Tempo al decesso nel corso dell’intera sperimentazione.
    *I timepoint settimana 52, settimana 76 e settimana 100 non saranno disponibili per tutti i pazienti.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) weeks 24 and 52
    2) weeks 24 and 52
    3) end of trial
    4) weeks 24, 52, 76, and 100
    5) weeks 24 and 52
    6) weeks 24 and 52
    7) weeks 24 and 52
    8) weeks 24 and 52
    9) week 24
    10) week 24
    11) end of trial
    12) end of trial
    13) end of trial
    1) settimana 24 e 52
    2) settimana 24 e 52
    3) nel corso dell’intera sperimentazione
    4) settimana 24, 52, 76 e 100
    5) settimana 24 e 52
    6) settimana 24 e 52
    7) settimana 24 e 52
    8) settimana 24 e 52
    9) settimana 24
    10) settimana 24
    11) nel corso dell’intera sperimentazione
    12) nel corso dell’intera sperimentazione
    13) nel corso dell’intera sperimentazione
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 trial5
    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 EEA28
    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
    Chile
    Colombia
    Czechia
    Denmark
    Finland
    France
    Germany
    Greece
    Hungary
    Italy
    Mexico
    Netherlands
    Norway
    Poland
    Portugal
    Russian Federation
    Spain
    Ukraine
    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 years2
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days21
    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: 10
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 20
    F.1.2Adults (18-64 years) No
    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 state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 14
    F.4.2.2In the whole clinical trial 30
    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)
    Patients who completed the treatment period according to protocol will
    be offered participation in a separate open label extension trial. The
    open label extension trial will be initiated if supported by the benefitrisk
    assessment from DBL 1 of the current trial.
    Ai pazienti che hanno completato il periodo di trattamento secondo il protocollo verrà offerto di partecipare ad una sperimentazione di estensione in aperto. Questa
    verrà avviata se supportata da risultati positivi di rischio/beneficio di questa sperimentazione.
    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 Decision2020-01-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-11-20
    P. End of Trial
    P.End of Trial StatusOngoing
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