Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    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).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2019-002053-33
    Sponsor's Protocol Code Number:TV48125-CNS-30082
    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:2021-06-14
    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 number2019-002053-33
    A.3Full title of the trial
    A Multicenter, Randomized, Double-Blind, Placebo-Controlled, ParallelGroup Study Comparing the Efficacy, Safety, and Tolerability of Subcutaneous Administration of Fremanezumab Versus Placebo for the Preventive Treatment of Chronic Migraine in Pediatric Patients 6 to 17 Years of Age
    Studio multicentrico, randomizzato, in doppio cieco, controllato con placebo, a gruppi paralleli, che confronta efficacia, sicurezza e tollerabilità della somministrazione sottocutanea di Fremanezumab verso Placebo per il trattamento preventivo di emicrania cronica in pazienti pediatrici da 6 a 17 anni di età
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Test if Fremanezumab is Effective in Preventing Chronic Migraine in Patients 6 to 17 Years of Age
    Studio volto a testare l’efficacia di fremanezumab nel prevenire l’emicrania cronica in pazienti di età compresa tra 6 e 17 anni
    A.3.2Name or abbreviated title of the trial where available
    SPACE
    SPACE
    A.4.1Sponsor's protocol code numberTV48125-CNS-30082
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/411/2019
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorTEVA BRANDED PHARMACEUTICAL PRODUCTS R&D, INC
    B.1.3.4CountryUnited States
    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 supportTeva Branded Pharmaceutical Products R&D, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerckle GmbH
    B.5.2Functional name of contact pointClinical Trial Information Desk
    B.5.3 Address:
    B.5.3.1Street AddressGraf-Arco-Str.3
    B.5.3.2Town/ cityUlm
    B.5.3.3Post code89079
    B.5.3.4CountryGermany
    B.5.6E-mailInfo.Era-clinical@teva.de
    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 AJOVY
    D.2.1.1.2Name of the Marketing Authorisation holderTEVA GmbH
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 namefremanezumab
    D.3.2Product code [TEV-48125]
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNfremanezumab
    D.3.9.1CAS number 1655501-53-3
    D.3.9.2Current sponsor codeTEV-48125
    D.3.9.4EV Substance CodeSUB181665
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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 AJOVY
    D.2.1.1.2Name of the Marketing Authorisation holderTEVA 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 namefremanezumab
    D.3.2Product code [TEV-48125]
    D.3.4Pharmaceutical form Solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNfremanezumab
    D.3.9.1CAS number 1655501-53-3
    D.3.9.2Current sponsor codeTEV-48125
    D.3.9.4EV Substance CodeSUB181665
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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 placeboSolution for injection in pre-filled syringe
    D.8.4Route of administration of the placeboSubcutaneous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection in pre-filled syringe
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic Migraine
    Emicrania cronica
    E.1.1.1Medical condition in easily understood language
    Chronic Migraine
    Emicrania cronica
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10066636
    E.1.2Term Chronic migraine
    E.1.2System Organ Class 100000004852
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLT
    E.1.2Classification code 10027603
    E.1.2Term Migraine headaches
    E.1.2System Organ Class 100000004852
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of fremanezumab as compared to placebo for the preventive treatment of chronic migraine (CM)
    Valutare l’efficacia di fremanezumab rispetto al placebo per il trattamento preventivo dell’emicrania cronica (CM).
    E.2.2Secondary objectives of the trial
    -To evaluate the safety and tolerability of fremanezumab in the
    preventive treatment of chronic migraine (CM)
    -To further demonstrate the efficacy of fremanezumab as compared to
    placebo for the preventive treatment of chronic migraine (CM)
    -To evaluate the immunogenicity of fremanezumab and the impact of
    antidrug antibodies (ADAs) on clinical outcomes in patients exposed to
    fremanezumab
    - valutare la sicurezza e la tollerabilità di fremanezumab nel trattamento preventivo dell’emicrania cronica (CM).
    - dimostrare ulteriormente l’efficacia di fremanezumab rispetto al placebo per il trattamento preventivo dell’emicrania cronica (CM).
    - valutare l’immunogenicità di fremanezumab e l’impatto degli anticorpi anti-farmaco (ADA) sugli esiti clinici nei pazienti esposti a fremanezumab.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    a. The patient is a male or female between the ages of 6 to 17 years
    (inclusive) on the day of randomization to study drug/IMP.
    b. The patient's parent(s) or legal guardian(s) must give written
    informed consent, and the patient must give assent (in accordance with
    local regulations). Note: In some countries, patients aged 15 to 17 years
    (inclusive) may give written informed consent; however, the patient's
    parent(s) or legal guardian(s) must be informed, per local regulations.
    c. The patient has a clinical history of recurrent headache consistent
    with the diagnosis of migraine for at least 6 months before screening,
    consistent with ICHD-3 criteria (Headache Classification Committee of
    the IHS 2013), and a history of =15 headache days per month, of which
    =8 headache days were assessed as migraine days per month in each of
    the 3 months prior to screening (visit 1).
    d. The patient or parent/caregiver has maintained a prospectively
    collected headache diary during a 28-day baseline period in which
    headache days were recorded on 15 or more days, and 8 or more of
    these headache days had 1 of the following migraine characteristics:
    -head pain of moderate to severe intensity lasting for 2 or more hours in duration and accompanied by either throbbing quality, predominantly
    unilateral location, or aggravation with normal activities.
    -headache is accompanied by a migraine-associated symptom, such as
    photophobia, phonophobia, abdominal pain, nausea, or vomiting.
    -headache is preceded by an aura, as described by ICHD-3 criteria.
    -headache was treated by a nonsteroidal anti-inflammatory drug
    (NSAID), triptan, or ergot preparation.
    e. The patient does not have chronic daily headache. For the purposes of
    this study, chronic daily headache is operationally defined as <4
    headache-free days during the 28-day baseline period.
    f. Not using preventive medications or using no more than 1 preventive
    medication for migraine or other medical condition, as long as the dose
    and regimen have been stable for at least 2 months prior to screening
    (visit 1).
    A person is considered to be not using preventive medications when at
    least 5 half-lives have passed since the last use of the medication prior
    to screening (visit 1) or at least 4 months have passed since the last use
    of Onabotulinum toxin A or B prior to screening (visit 1).
    g. Females who are postmenarchal or =12 years of age may be included
    only if they have a negative beta-human chorionic gonadotropin (ß-HCG)
    test at baseline or are sterile.
    h. Females who are postmenarchal or =12 years of age and sexually
    active must use highly effective birth control methods with their male
    partners for the duration of the study (ie, starting at screening) and for
    6 months after the last dose of IMP. Males who are sexually active with
    female partners must use a condom for the duration of the study and for
    6 months after the last administration of IMP.
    i. The patient/caregiver has demonstrated compliance with the
    electronic headache diary during the 28-day baseline period by entry of
    headache data on a minimum of 21 out of 28 days (approximately 75%
    diary compliance).
    j. The patient is in good health, as determined by a medical and
    psychiatric history, medical examination, 12-lead ECG, serum chemistry,
    hematology, coagulation, urinalysis, and serology.
    k. The patient/caregiver must be willing and able to comply with study
    requirements and return to the clinic as required for the duration of the
    study.
    l. The patient weighs at least 17.0 kg on the day of randomization to
    study drug/IMP.
    m. The patient has a body mass index ranging from the 5th to the 95th
    percentile, inclusive, at screening.
    n. The patient has received all recommended age-appropriate vaccines
    according to local standard of care and schedule prior to screening.
    a. Il paziente è un soggetto di sesso maschile o femminile di età compresa tra 6 e 17 anni (inclusi) il giorno della randomizzazione al medicinale in studio/IMP.
    b. Il(I) genitore(i) o il(i) tutore(i) legale(i) del/della paziente deve fornire il consenso informato scritto e il/la paziente deve fornire l’assenso (in conformità ai regolamenti locali).
    Nota: in alcuni paesi i pazienti di età compresa tra 15 e 17 anni (compresi) potranno fornire il consenso informato scritto; tuttavia il(i) genitore(i) o il(i) tutore(i) legale(i) del/della paziente deve/devono essere informato/i, come da normativa locale.
    c. Il paziente presenta un’anamnesi clinica di cefalea ricorrente coerente con la diagnosi di emicrania per almeno 6 mesi prima dello screening, in conformità ai criteri ICHD-3 (Comitato di classificazione delle cefalee dell’IHS 2013) e un'anamnesi di =15 giorni con cefalea al mese, di cui =8 giorni con cefalea valutati come giorni con emicrania al mese in ciascuno dei 3 mesi precedenti lo screening (Visita 1).
    d. Il paziente o il genitore/caregiver ha mantenuto un diario della cefalea con raccolta prospettica durante un periodo basale di 28 giorni in cui i giorni con cefalea sono stati annotati su 15 o più giorni, e 8 o più di tali giorni con cefalea avevano 1 delle seguenti caratteristiche dell’emicrania:
    - dolore alla testa di intensità da moderata a grave che si protrae per 2 o più ore ed è accompagnato da qualità pulsante, posizione principalmente unilaterale, o aggravamento nelle normali attività.
    - la cefalea è accompagnata da un sintomo associato all’emicrania, come fotofobia, fonofobia, dolore addominale, nausea o vomito.
    - la cefalea è preceduta da un’aura, come descritto dai criteri ICHD-3.
    - la cefalea è stata trattata con un farmaco antinfiammatorio non steroideo (FANS), o un medicinale a base di triptano o di alcaloidi della segale cornuta.
    e. Il paziente non ha cefalea quotidiana cronica. Agli scopi di questo studio, la cefalea quotidiana cronica è definita dal punto di vista gestionale come <4 giorni liberi da cefalea durante il periodo basale di 28 giorni.
    f. Il paziente non utilizza medicinali preventivi o utilizza non più di 1 medicinale preventivo per l’emicrania o altre condizioni mediche, a condizione che la dose e il regime siano stabili da almeno 2 mesi prima dello screening (Visita 1). Nell’Allegato C è incluso un elenco dei medicinali preventivi consentiti per l’emicrania.
    Nota: una persona viene considerata come non utilizzatrice di medicinali preventivi se sono passate almeno 5 emivite dall’ultimo utilizzo del medicinale prima dello screening (Visita 1) o almeno 4 mesi dall’ultimo utilizzo di tossina botulinica di tipo A
    o B prima dello screening (Visita 1).
    g. I soggetti di sesso femminile che hanno già le mestruazioni o di età =12 anni possono essere inclusi solo se hanno un test della beta-gonadotropina corionica umana (ß-HCG) negativo al basale o sono sterili. Nell’Allegato G sono fornite le definizioni di soggetti di sesso femminile in età fertile e soggetti di sesso femminile non in età fertile.
    h. I soggetti di sesso femminile che hanno già le mestruazioni o di età =12 anni e sessualmente attivi devono utilizzare metodi contraccettivi altamente efficaci con i propri partner di sesso maschile per la durata dello studio (cioè a partire dallo screening) e per 6 mesi dopo l’ultima dose dell’IMP. I soggetti di sesso maschile che sono sessualmente attivi con le proprie partner di sesso femminile devono utilizzare un profilattico per la durata dello studio e per 6 mesi dopo l’ultima somministrazione dell’IMP. Nell’Allegato G sono inclusi ulteriori dettagli.

    Spazio esaurito. Fare riferimento alla sinossi.
    E.4Principal exclusion criteria
    a. The patient is using medications containing opioids (including
    codeine) or barbiturates (including Fiorinal®, Fioricet®, or any other
    combination containing butalbital) for the treatment of migraine during
    the 3 months prior to the day of the screening visit.
    b. The patient has used an intervention/device (eg, scheduled nerve
    block or transcranial magnetic stimulation) for the treatment of migraine
    during the 2 months prior to the day of the screening visit.
    c. The patient has any clinically significant cardiovascular (including
    congenital cardiac anomalies or thromboembolic events), endocrine,
    gastrointestinal, genitourinary, hematologic, hepatic, immunologic,
    neurologic, ophthalmic, pulmonary, renal disease, or complications of an
    infection, at the discretion of the investigator.
    d. The patient has a current history of a clinically significant psychiatric condition, any prior history of a suicide attempt, or a history of suicidal
    ideation with a specific plan within the past 2 years, at the discretion of
    the investigator.
    e. The patient has an ongoing infection or a known history of human
    immunodeficiency virus infection, tuberculosis, Lyme disease, chronic
    hepatitis B or C, or a known active infection of COVID-19.
    f. The patient has a past or current history of cancer.
    g. The patient is pregnant, nursing or taking a combined estrogen and
    progestogen hormonal contraceptive.
    h. The patient has a history of hypersensitivity reactions to injected
    proteins, including monoclonal antibodies (mAbs), or a history of
    Stevens-Johnson Syndrome or toxic epidermal necrolysis syndrome, or
    the patient is concomitantly using lamotrigine.
    i. The patient has participated in another study of an IMP (or a medical
    device) within the 30 days (or 90 days for biologics) or 5 half-lives
    previous to the day of the screening visit (whichever is longer), or is
    currently participating in another study of an IMP (or a medical device).
    j. The patient has had exposure to a mAb targeting the calcitonin generelated peptide (CGRP) pathway (erenumab, eptinezumab, galcanezumab, fremanezumab) during the 6 months previous to the day of the screening visit.
    k. Previous participation in the Phase 1 pharmacokinetics study (Study TV48125-CNS-10141).
    l. In the judgment of the investigator, the patient has an abnormal finding on the baseline 12-lead ECG considered clinically significant.
    m. In the judgment of the investigator, the patient has a significantly abnormal finding during the 28-day baseline period, including hematology, blood chemistry, coagulation tests, or urinalysis values/findings (abnormal tests may be repeated for confirmation).
    n. The patient has hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP]) more than 1.5× the upper limit of normal (ULN) during the 28-day baseline period, after confirmation in a repeat test, or suspected hepatocellular damage that fulfills the criteria for Hy's
    law.
    o. The patient has serum creatinine more than 1.5× the ULN, clinically significant proteinuria (urine dipstick +4), an estimated glomerular filtration rate of <90 mL/min/1.73m2, as calculated by the Schwartz formula (CrCl=[k×Ht]/Serum Creatinine), or evidence of renal disease during the 28-day baseline period.
    p. The patient has any history of alcohol or drug abuse.

    Spazio esaurito, fare riferimento al Protocollo per ulteriori criteri.
    . Il/La paziente utilizza medicinali contenenti oppioidi (inclusa codeina) o barbiturici (inclusi Fiorinal®, Fioricet® o qualsiasi altra combinazione contenente butalbital) per il trattamento dell’emicrania nei 3 mesi precedenti il giorno della visita di screening.
    b. Il/La paziente ha utilizzato un intervento/dispositivo (es. blocco nervoso programmato o stimolazione magnetica transcranica) per il trattamento dell’emicrania nei 2 mesi precedenti il giorno della visita di screening.
    c. Il/La paziente ha una patologia renale, polmonare, oftalmica, neurologica, immunologica, epatica, ematologica, genitourinaria, gastrointestinale, endocrina o cardiovascolare clinicamente significativa (inclusi eventi tromboembolici o anomalie cardiache congenite), o complicanze causate da un’infezione, a discrezione dello Sperimentatore.
    d. Il/La paziente ha un’anamnesi attuale di condizione psichiatrica clinicamente significativa, qualsiasi anamnesi antecedente di tentativo di suicidio o di ideazione suicidiaria con un piano specifico entro gli ultimi 2 anni a discrezione dello sperimentatore.
    e. Il/La paziente ha un’infezione in corso oppure un’anamnesi nota di infezione da virus dell’immunodeficienza umana, tubercolosi, malattia di Lyme oppure epatite cronica B o C o un’infezione nota attiva di COVID-19.
    f. Il/La paziente ha un’anamnesi passata o attuale di cancro.
    g. La paziente è in stato di gravidanza, in allattamento o sta prendendo un contraccettivo ormonale combinato estrogeno-progestinico.
    h. Il/La paziente ha un’anamnesi di reazioni da ipersensibilità alle proteine iniettate, inclusi gli anticorpi monoclonali (mAb), o un’anamnesi di Sindrome di Stevens-Johnson o di necrolisi epidermica tossica, o il/la paziente sta usando contemporaneamente lamotrigina.
    i. Il/La paziente ha partecipato a un altro studio di un IMP (o un dispositivo medico) nei 30 giorni (o 90 giorni per medicinali biologici) o 5 emivite precedenti il giorno della visita di screening (a seconda del periodo più lungo) o sta attualmente partecipando a un altro studio di un IMP (o un dispositivo medico).
    j. Il/La paziente ha avuto un'esposizione a un mAb che agisce sulla via biochimica del peptide correlato al gene della calcitonina (CGRP) (erenumab, eptinezumab, galcanezumab, fremanezumab) nei 6 mesi precedenti il giorno della visita di screening.
    k. Partecipazione precedente allo studio di farmacocinetica di Fase 1
    (studio TV48125-CNS-10141).
    l. Secondo il parere dello Sperimentatore, il/la paziente presenta un riscontro anomalo sull’ECG a 12 derivazioni basale considerato clinicamente significativo.
    m. Secondo il parere dello Sperimentatore, il/la paziente presenta un riscontro anomalo significativo durante il periodo basale di 28 giorni, inclusi valori/riscontri di ematologia, chimica del sangue, test di coagulazione o analisi delle urine (i test anomali possono essere ripetuti per conferma).
    n. Il/La paziente ha enzimi epatici (alanina aminotransferasi [ALT], aspartato aminotransferasi [AST], fosfatasi alcalina [ALP]) superiori a 1,5× limite superiore della norma (LSN) durante il periodo basale di 28 giorni, dopo conferma in un test ripetuto o un danno epatocellulare sospetto che soddisfa i criteri per la legge di Hy.
    Il/La paziente ha livelli di creatinina sierica superiori a 1,5x LSN, proteinuria clinicamente significativa (striscia reattiva delle urine +4), un tasso di filtrazione glomerulare stimato di <90 mL/min/1,73m2 calcolato in base alla formula di Schwartz (CrCl = [k × Ht]/creatinina sierica), o evidenza di patologia renale durante il periodo basale di 28 giorni.
    p. Il/La paziente ha qualsiasi anamnesi di abuso di alcol o droga.

    Spazio esaurito, fare riferimento al Protocollo per ulteriori criteri.
    E.5 End points
    E.5.1Primary end point(s)
    Mean change from baseline (28-day baseline period) in the monthly
    average number of headache days of at least moderate severity during
    the 12-week period after the first dose of study drug
    Cambiamento medio dal basale (periodo basale di 28 giorni) nel numero medio mensile di giorni con cefalea di gravità almeno moderata durante il periodo di 12 settimane dopo la prima dose del medicinale in studio.
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 weeks after the first dose of study drug
    12 settimane dopo la prima dose del farmaco in studio.
    E.5.2Secondary end point(s)
    Efficacy endpoints:
    -Mean change from baseline (28-day baseline period) in monthly
    average number of migraine days during the 12-week period after the
    first dose of study drug
    -Proportion of patients reaching at least 50% reduction in the monthly
    average number of headache days of at least
    moderate severity during the 12-week period after the first dose of
    study drug
    -Mean change from baseline (28-day baseline period) in the
    monthly average number of days of use of any acute headache
    medications during the 12-week period after the first dose of study drug
    -Mean change from baseline (day 1) in migraine-related disability score,
    as measured by the Pediatric Migraine Disability Assessment
    (PedMIDAS) questionnaire, at 12 weeks after administration of the first
    dose of study drug
    -Mean change from baseline (day 1) in quality of life, as measured by the
    Pediatric Quality of Life Inventory (PedsQL), at 12 weeks after
    administration of the first dose of study drug
    -Proportion of patients developing antidrug antibodies (ADAs)
    throughout the study. The impact of ADAs on safety and efficacy will be
    analyzed if the number of ADA-positive
    patients allows
    Safety and tolerability endpoints:
    -Occurrence of adverse events throughout the study, including local
    injection site reaction/pain
    -Abnormal standard 12-lead electrocardiogram (ECG) findings
    -Changes from baseline in vital signs (systolic and diastolic blood
    pressure, pulse, temperature, and respiratory rate), height, and weight
    measurements
    -Changes from baseline in clinical laboratory (serum chemistry,
    hematology, coagulation, and urinalysis) test results
    -Abnormal physical examination findings
    -Suicidal ideation and behavior as suggested by the Columbia-Suicide
    Severity Rating Scale (C-SSRS)
    Gli endpoint di efficacia secondari sono i seguenti:
    · cambiamento medio dal basale (periodo basale di 28 giorni) nel numero medio mensile di giorni con emicrania durante il periodo di 12 settimane dopo la prima dose del medicinale in studio
    · proporzione di pazienti che raggiungono una riduzione pari ad almeno il 50% nel numero medio mensile di giorni con cefalea di gravità almeno moderata durante il periodo di 12 settimane dopo la prima dose del medicinale in studio
    · cambiamento medio dal basale (periodo basale di 28 giorni) nel numero medio mensile di giorni di utilizzo di eventuali medicinali per cefalea acuta durante il periodo di 12 settimane dopo la prima dose del medicinale in studio
    · cambiamento medio dal basale (Giorno 1) nel punteggio di disabilità legata all’emicrania, misurata dal questionario Pediatric Migraine Disability Assessment (PedMIDAS),12 settimane dopo la somministrazione della prima dose del medicinale in studio

    · cambiamento medio dal basale (Giorno 1) nella qualità della vita, misurata dal Pediatric Quality of Life Inventory(PedsQL), 12 settimane dopo la somministrazione della prima dose del medicinale in studio

    · proporzione di pazienti che sviluppano anticorpi anti-farmaco (ADA) nel corso dello studio. Se il numero di pazienti positivi agli ADA lo consente, sarà analizzato l’impatto degli ADA sulla sicurezza e l’efficacia.

    Gli endpoint di sicurezza e tollerabilità sono i seguenti:
    · comparsa di eventi avversi nel corso dello studio, tra cui reazione/dolore nella sede di iniezione locale
    · riscontri anomali nell’elettrocardiogramma (ECG) a 12 derivazioni standard
    · cambiamenti dal basale nelle misurazioni dei segni vitali (pressione arteriosa sistolica e diastolica, polso, temperatura e requenza respiratoria), dell'altezza e del peso
    · cambiamenti dal basale nei risultati dei test clinici di laboratorio (chimica sierica, ematologia, coagulazione, e analisi delle urine)
    · riscontri anomali nell'esame obiettivo
    · Ideazione e comportamento suicidari come suggerito dalla Columbia-Suicide Severity Rating Scale (C-SSRS)
    E.5.2.1Timepoint(s) of evaluation of this end point
    -Mean change from baseline in monthly average number of migraine
    days : week 12 after first dose of study drug
    -Proportion of patients reaching at least 50% reduction in the monthly
    average number: week 12 after first dose of study drug
    -Mean change from baseline in the monthly average number of days of
    use if any acute headache medications: week 12 after first dose of study
    drug
    -Mean change from baseline (day 1) in migraine-related disability score:
    week 12 after first dose of study drug
    -Mean change from baseline in quality of life: week 12 after first dose of
    study drug
    -Proportion of patients developing ADAs: week 12 after first dose of
    study drug

    Safety and tolerability: throughout the study
    -Variazione media rispetto al basale del numero mensile medio di giorni di emicrania: settimana 12 dopo la prima dose
    -Proporzione di pazienti che raggiungono riduzione di almeno il 50% del num. medio mensile: settimana 12 dopo la prima dose
    -Variazione media rispetto al basale del num. mensile medio di giorni di eventuale assunzione di medicinali per la cefalea acuta: settimana 12 dopo la prima dose
    -Variazione media rispetto al basale (giorno 1) del punteggio di disabilità legata all’emicrania: settimana 12 dopo la prima dose
    -Variazione media rispetto al basale della qualità della vita: settimana 12 dopo la prima dose del farmaco in studio
    -Proporzione di pazienti che sviluppano ADA: settimana 12 dopo la prima dose del farmaco in studio

    Sicurezza e tollerabilità: per tutto lo studio
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    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 Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    Tollerabilità
    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 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 trial4
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    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
    Finland
    Germany
    Israel
    Italy
    Netherlands
    Poland
    Spain
    E.8.7Trial has a data monitoring committee No
    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 years4
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    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: 104
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 314
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Patients are minors
    I pazienti sono minorenni.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state71
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 165
    F.4.2.2In the whole clinical trial 418
    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)
    Upon completion of the final study assessments, all eligible patients
    will be offered enrollment in a long-term safety and tolerability study
    (Study TV48125-CNS-30084), consisting of 9 months (36 weeks) of
    open-label treatment and 5 months of follow-up commencing from the
    last study drug administration.
    Una volta completate le valutazioni finali dello studio, a tutti i pazienti idonei
    sarà offerto l’arruolamento in uno studio di sicurezza e tollerabilità a lungo termine (Studio TV48125-CNS-30084), articolato in 9 mesi (36 settimane) di trattamento in aperto e 5 mesi di follow-up a partire dall’ultima somministrazione del farmaco in studio.
    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 Decision2020-08-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-09-08
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2023 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA