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    Summary
    EudraCT Number:2021-000007-21
    Sponsor's Protocol Code Number:212620
    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:2021-08-17
    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 number2021-000007-21
    A.3Full title of the trial
    A two-part, randomized, placebo controlled, double blind, multicenter, Phase 3 study to evaluate the efficacy and safety of linerixibat for the treatment of cholestatic pruritus in participants with primary biliary cholangitis (PBC).
    Studio in due parti, randomizzato, controllato verso placebo, in doppio cieco, multicentrico, di Fase 3 per valutare l’efficacia e la sicurezza di linerixibat per il trattamento del prurito colestatico nei partecipanti con colangite biliare primitiva (PBC).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Global Linerixibat Itch STudy of Efficacy and Safety iN PBC (GLISTEN)
    Studio globale di efficacia e sicurezza di linerixibat per il prurito nella PCB (GLISTEN)
    A.3.2Name or abbreviated title of the trial where available
    PH3a,linerixibat vsPBO,efficacy&safety,itch study for the treatment of cholestatic pruritus in PBC
    PH3a, linerixibat vsPBO, efficacia e sicurezza, studio sul prurito per il trattamento di prurito col
    A.4.1Sponsor's protocol code number212620
    A.5.4Other Identifiers
    Name:GLISTENNumber:GLISTEN
    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 SponsorGLAXOSMITHKLINE RESEARCH AND DEVELOPMENT
    B.1.3.4CountryUnited Kingdom
    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 supportGlaxoSmithKline, Reseach and Development Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline Research & Development Ltd
    B.5.2Functional name of contact pointClinical Trials Helpdesk Support
    B.5.3 Address:
    B.5.3.1Street Address980 Great West Road
    B.5.3.2Town/ cityBrentford, Middlesex
    B.5.3.3Post codeTW8 9GS
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number004408007839733
    B.5.5Fax number0000000
    B.5.6E-mailGSKClinicalSupportHD@gsk.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 nameLinerixibat
    D.3.2Product code [GSK2330672]
    D.3.4Pharmaceutical form Film-coated tablet
    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 INNLinerixibat
    D.3.9.1CAS number 1345983-37-0
    D.3.9.2Current sponsor codeGSK2330672
    D.3.9.3Other descriptive name3-({[(3R,5R)-3-butyl-3-ethyl-7-(methyloxy)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro- 1,4-benzothiazepin-8-yl]methyl}amino)pentanedioic acid
    D.3.9.4EV Substance CodeSUB194569
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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 placeboFilm-coated tablet
    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
    Moderate to severe Cholestatic pruritus with primary biliary cholangitis (PBC).
    Prurito colestatico da moderato a severo con colangite biliare primitiva (PBC).
    E.1.1.1Medical condition in easily understood language
    Moderate to Severe itch (Pruritus) in patients with primary biliary cholangitis (PBC)
    Prurito da moderato a severo in pazienti con colangite biliare primitiva (CBP)
    E.1.1.2Therapeutic area Diseases [C] - Digestive System Diseases [C06]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10064190
    E.1.2Term Cholestatic pruritus
    E.1.2System Organ Class 10040785 - Skin and subcutaneous tissue disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10080429
    E.1.2Term Primary biliary cholangitis
    E.1.2System Organ Class 10019805 - Hepatobiliary disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To investigate the effect of treatment with oral linerixibat compared with placebo on itch in PBC patients with cholestatic pruritus over 24 weeks (Part A)
    Studiare l’effetto del trattamento con linerixibat per via orale rispetto a placebo sul prurito in pazienti PBC con prurito colestatico nel corso di 24 settimane (Parte A)
    E.2.2Secondary objectives of the trial
    To evaluate the early effects of oral linerixibat compared to placebo on itch in PBC patients with cholestatic pruritus (Part A)
    To characterize the effects of treatment with oral linerixibat compared with placebo on health related QoL(Part A)
    To evaluate the effects of 24 weeks of treatment with oral linerixibat compared to placebo on itch response rates in PBC patients with
    cholestatic pruritus (Part A)
    To investigate the treatment effect of oral linerixibat compared with placebo on Patient's Global Impression of Severity (PGI-S) and Patient's Global Impression of Change (PGI-C) throughout the treatment period (Part A)
    To evaluate the effects of treatment with linerixibat on markers of PBC disease activity and progression (Part A )
    Safety
    To evaluate the safety of oral linerixibat compared with placebo (Part A and Part B)
    Valutare gli effetti precoci di linerixibat per via orale rispetto a placebo sul prurito in pazienti PBC con prurito colestatico (Parte A)
    Caratterizzare gli effetti del trattamento con linerixibat per via orale rispetto a placebo sulla QoL correlata alla salute (Parte A)
    Valutare gli effetti di 24 settimane di trattamento con linerixibat per via orale rispetto a placebo sui tassi di risposta per il prurito in pazienti PBC con prurito colestatico (Parte A)
    Studiare l’effetto del trattamento con linerixibat per via orale rispetto a placebo sugli indici Patient’s Global Impression of Severity (PGI-S) e Patient’s Global Impression of Change (PGI-C) per tutto il periodo di trattamento (Parte A)
    Valutare gli effetti del trattamento con linerixibat sui marker di attività di malattia e di progressione della PCB (Parte A)
    Sicurezza
    Valutare la sicurezza di linerixibat per via orale rispetto a placebo (Parte A e Parte B)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Participants are eligible to be included in the study only if all of the following criteria apply:
    Sex and Age
    1. Male and female participants must be between 18 to 80 years of age inclusive, at the time of signing the informed consent.
    Note: if country/site age requirements for consent differ, the more stringent (e.g., higher age) restriction will be required for that country/site.
    Type of Participant and Disease Characteristics
    2. Participants who have proven PBC, as demonstrated by historically having at least 2 of the following:
    • Documented history of sustained increased ALP levels greater than ULN first recognized at least 6 months prior to the Screening Visit (Note: Sustained ALP elevations at the time of Screening is not required, recognizing that the ALP may have decreased after initiation of UDCA therapy).
    • Documented positive anti-mitochondrial antibody (AMA) titer (>1:40 titer on immunofluorescence or M2 positive by enzyme linked immunosorbent assay [ELISA]) or PBC-specific antinuclear antibodies (antinuclear dot and/or nuclear rim positive).
    • Liver biopsy (documented at any time in the past) consistent with PBC.
    3. Participants who, during the Screening period, record their daily itch score by entering at least 40 of the 56 required itch entries, with an entry on at least 4 days in each week, during the 4-week period immediately preceding Randomization at Day 1 and have a Monthly Itch Score of =4 (i.e., at least 1 of the 4 weekly Mean Worst Daily Itch Scores must be =4), and no Mean Worst Daily Itch Score can be <3 for any other week.
    Contraceptive/Barrier Requirements
    4. Contraceptive/Barrier Requirements (applicable for female participants only): A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
    o Is not a woman of non-childbearing potential
    OR
    o Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method as described in Section 10.4 during the study intervention period (at a minimum until 4 weeks after the last dose of study intervention).
    The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention.
    • A WOCBP must have a negative highly sensitive urine pregnancy test (or serum as required by local regulations) within 7 days before the first dose of study intervention, see Section 8.2.5 Pregnancy Testing.
    • Additional requirements for pregnancy testing during and after study intervention are located in Section 8.2.5.
    • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy
    Note: Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
    • Full requirements for pregnancy testing during and after study intervention are located in Section 10.4 Appendix 4.
    Informed Consent
    5. Capable of giving signed informed consent as described in Section 10.1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
    1.Partecipanti di sesso maschile e femminile di età compresa tra 18 e 80 anni (estremi inclusi) al momento della firma del consenso informato
    Nota: se i requisiti nazionali/del centro relativi all’età differiscono da quanto specificato, per quel Paese/centro sarà richiesta la restrizione più stringente (ad es. età superiore)
    2.Partecipanti affetti da PBC comprovata, dimostrata dalla presenza storica di almeno 2 dei seguenti:
    •Anamnesi documentata di aumento sostenuto di livelli di ALP superiori al limite superiore di normalità (ULN) identificato per la prima volta almeno 6 mesi prima della Visita di screening [Nota: al momento dello Screening non sono richiesti aumenti sostenuti di ALP, poiché si riconosce che l’ALP potrebbe essere diminuita dopo l’inizio della terapia con acido ursodesossicolico (UDCA)].
    •Titolo anticorpale anti-mitocondriale (AMA) positivo documentato [titolo >1:40 all'immunofluorescenza o M2 positivo da saggio immunoassorbente legato all’enzima (ELISA) o anticorpi antinucleo specifici della PBC (punto antinucleo e/o bordo nucleare positivo].
    •Biopsia epatica (documentata in qualsiasi momento nel passato) coerente con PBC.
    3.Partecipanti che, durante il periodo di Screening, registrano il loro punteggio giornaliero per il prurito inserendo almeno 40 delle 56 voci relative al prurito richieste, con una voce per almeno 4 giorni in ciascuna settimana, durante il periodo di 4 settimane immediatamente precedente la randomizzazione al Giorno 1 e con un punteggio del prurito mensile =4 (ovvero, almeno 1 dei 4 punteggi settimanali del prurito giornaliero peggiore deve essere =4) e nessun punteggio medio del peggior prurito giornaliero può essere <3 per qualsiasi altra settimana.
    4.Requisiti relativi ai metodi contraccettivi/di barriera (applicabili solo per le partecipanti di sesso femminile): una partecipante di sesso femminile è idonea alla partecipazione se non è in gravidanza o allattamento, e se si applica una delle seguenti condizioni:
    o Si tratta di una donna non potenzialmente fertile (WONCBP)
    OPPURE
    o Si tratta di una donna potenzialmente fertile (WOCBP) e utilizza un metodo contraccettivo accettabile come descritto nella Sezione 10.4 durante il periodo di trattamento in studio (e almeno fino a 4 settimane dopo l’ultima somministrazione del trattamento in studio). Lo sperimentatore dovrebbe valutare il potenziale di insuccesso del metodo contraccettivo (ad es. mancata aderenza, inizio recente) in relazione alla somministrazione della prima dose di trattamento in studio
    Una WOCBP deve avere un test di gravidanza ad elevata sensibilità (sulle urine o sul siero come richiesto dalle normative locali) negativo nei 7 giorni precedenti la prima somministrazione di trattamento in studio. Fare riferimento alla Sez. 8.2.5 “Pregnancy Testing”.
    o Se un test di gravidanza sulle urine non può essere confermato come negativo (ad esempio il risultato è ambiguo), è richiesto un test di gravidanza sul siero. In tali casi, la partecipante deve essere esclusa dalla partecipazione se il risultato del test di gravidanza sul siero è positivo.
    o La Sez. 8.2.5 riporta ulteriori requisiti relativi ai test di gravidanza durante e dopo il trattamento in studio.
    o Lo sperimentatore è responsabile della revisione dell’anamnesi, dell’anamnesi mestruale e dell’attività sessuale recente al fine di diminuire il rischio di inclusione di una donna in stato di gravidanza precoce non rilevata.
    Nota: l’utilizzo di metodi contraccettivi da parte delle donne deve essere coerente con le normative locali sui metodi contraccettivi per i partecipanti agli studi clinici. La Sez. 10.4 Appendice 4 riporta i requisiti completi relativi ai test di gravidanza durante e dopo il trattamento in studio.
    5. Partecipanti in grado di dare il proprio consenso informato come descritto nella Sez. 10.1, che comprende la conformità ai requisiti e alle restrizioni elencate nel consenso informato e nel Protocollo.
    E.4Principal exclusion criteria
    1. Participants with symptoms suggestive of active COVID-19 infection (i.e. fever,cough, loss of taste or smell etc.) are excluded whilst symptoms persist.
    2. Total bilirubin >2.0 x ULN using the average of two baseline measures.
    3. Screening ALT > 6x ULN in a single baseline measure or ALT > 5x ULN using the average of two baseline measures.
    4. Participants with abnormal liver biochemistry (ALT, aspartate aminotransferase [AST], ALP, or total bilirubin) during the Screening period (at Visit 1 or Visit 2) and the variance between these two samples for the abnormal parameter is >40%.
    5. Screening estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 based on CKD-EPI equation.
    6. History or presence of hepatic decompensation (e.g., variceal bleeding, hepatic encephalopathy or ascites).
    7. Presence of actively replicating viral hepatitis B or C (HBV, HCV) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease and/or confirmed hepatocellular carcinoma or biliary cancer.
    8. Infection with human immunodeficiency virus (HIV)
    9. Current clinically significant diarrhea in the Investigator's medical opinion.
    10. Active inflammatory ileal disease according to Investigator´s clinical judgment.
    11. Current symptomatic cholelithiasis or cholecystitis.
    12. Current diagnosis of primary skin disorders with itch symptoms (e.g.,atopic dermatitis, psoriasis).
    13. Primary sleep disorders such as but are not limited to sleep apnea,narcoleptsy,hypersomnia
    14. Any current malignancies (including hematologic and solid malignancies).
    15. Current/previous diagnosis of colorectal cancer.
    16. History of bariatric surgery with ileal bypass at any time, or any bariatric surgery performed in the past 3 years
    17. Any current uncontrolled psychiatric condition
    18. Any current medical condition (e.g. senility or dementia), which may affect the participant's ability to comply with the protocol specified procedures.
    Prior/Concomitant Therapy
    19. Initiation, discontinuation or change in dose of UDCA in the 8 weeks prior to Screening
    20. Use of obeticholic acid: within 8 weeks prior to Screening
    21. Initiation, discontinuation or change in dose of bezafibrate or fenofibrate at any time during the 8 weeks prior to Screening.
    22. Initiation, discontinuation, or change in dose of any of the following in the 8 weeks prior to Screening: bile acid binding resins, rifampicin, naltrexone, naloxone, nalfurafine, pregabalin, gabapentin, sertraline or other SSRIs.
    23. Initiation, discontinuation or change in dose of opioids, regardless of indication, in the 8 weeks prior to Screening.
    24. Initiation, discontinuation or change in dose of colchicine, methotrexate ,azathioprine, or systemic corticosteroids in the 8 weeks prior to Screening
    25. Initiation, discontinuation, or change in dose of antihistamines used for the treatment of itching the 8 weeks prior to Screening.
    Condizioni mediche
    1. I partecipanti con sintomi suggestivi di infezione attiva da COVID-19 (ovvero febbre, tosse, perdita del gusto o dell’olfatto, ecc.) sono esclusi fino a che permangono i sintomi.
    2. Bilirubina totale >0 x ULN utilizzando la media di due misurazioni basali.
    3. ALT > 6x ULN allo Screening ad una singola misurazione basale oppure ALT > 5x ULN utilizzando la media di due misurazioni basali.
    4. Partecipanti con biochimica epatica anormale (ALT, aspartato aminotransferasi [AST], ALP, o bilirubina totale) durante il periodo di Screening (alla Visita 1 o alla Visita 2) e la varianza tra questi due campioni per il parametro anormale è >40%.
    5. Velocità di filtrazione glomerulare stimata (estimated Glomerular Filtration Rate - eGFR) <30 mL/min/1,73m2 basato sull'equazione CKD-EPI allo Screening.
    6.Anamnesi o presenza di scompenso epatico (ad esempio emorragia varicosa, encefalopatia epatica o ascite).
    7.Presenza di infezione da epatite virale B o C (HBV, HCV) che replica attivamente, colangite sclerosante primitiva (PSC), malattia epatica alcolica e/o carcinoma epatocellulare o cancro biliare confermato.
    8.Infezione da virus dell’immunodeficienza umana (Human Immunodeficiency Virus - HIV)
    9.Attuale diarrea clinicamente significativa secondo il parere medico dello sperimentatore.
    10.Malattia infiammatoria attiva dell’ileo a giudizio clinico dello sperimentatore.
    11.Attuale colelitiasi sintomatica o colecistite.
    12. Diagnosi attuale di disturbi cutanei primari della pelle con sintomi di prurito (ad esempio, dermatite atopica, psoriasi).
    13.Disturbi primari del sonno quali, a titolo esemplificativo ma non esaustivo, apnea, narcolessia, ipersonnia.
    14. Qualsiasi patologia maligna in corso (incluse neoplasie maligne ematologiche e solide).
    15. Diagnosi attuale/pregressa di carcinoma del colon-retto.
    16.Anamnesi di chirurgia bariatrica con bypass dell’ileo in qualsiasi momento, o qualsiasi chirurgia bariatrica eseguita negli ultimi 3 anni.
    17. Qualsiasi condizione psichiatrica non controllata attuale
    18. Qualsiasi condizione medica attuale (ad esempio senilità o demenza), che può influire sulla capacità del partecipante di rispettare le procedure specificate nel protocollo.
    Terapie pregresse/concomitanti
    19.Inizio, interruzione o variazione della dose di UDCA nelle 8 settimane precedenti lo Screening
    20.Utilizzo di acido obeticolico nelle 8 settimane precedenti lo Screening.
    21.Inizio, interruzione o variazione della dose di bezafibrato o fenofibrato in qualsiasi momento nelle 8 settimane precedenti lo Screening
    22. Inizio, interruzione o variazione della dose di uno qualsiasi dei seguenti nelle 8 settimane precedenti lo Screening: resine che legano gli acidi biliari, rifampcina, naltrexone, naloxone, nalfurafina, pregabalin, gabapentin, sertralina o altri inibitori selettivi della ricaptazione della serotonina
    23. Inizio, interruzione o variazione di dose di oppioidi, indipendentemente dall’indicazione, nelle 8 settimane precedenti lo Screening (i partecipanti possono essere inseriti nello studio se in trattamento con dosi stabili di tali farmaci).
    24. Inizio, interruzione o variazione di dose di colchicina, metotrexato, azatioprina o corticosteroidi sistemici nelle 8 settimane precedenti lo Screening.
    25. Inizio, interruzione o variazione di dose di antistaminici utilizzati per il trattamento del prurito nelle 8 settimane precedenti lo Screening.
    E.5 End points
    E.5.1Primary end point(s)
    Change from Baseline in Monthly Itch Scores over 24 weeks using a 0-10 numerical rating scale (NRS)
    Variazione rispetto al basale nei punteggi mensili del prurito nel corso di 24 settimane utilizzando una NRS 0-10
    E.5.1.1Timepoint(s) of evaluation of this end point
    Itch data will be collected daily from Screening through Week 32
    I dati sul prurito verranno raccolti quotidianamente dallo screening fino alla settimana 32
    E.5.2Secondary end point(s)
    • Change from baseline in Mean Worst Daily Itch score at Week 2
    • Change from Baseline in Monthly Sleep Score as measured by 0-10 NRS over 24 weeks
    • Change from Baseline in PBC-40 domain scores at Week 24
    • Responder defined as achieving a =2-point reduction from Baseline in the Monthly Itch score at Week 24.
    • Responder defined as achieving a =3-point reduction from Baseline in the Monthly Itch score at Week 24.
    • Responder defined as achieving a =4-point reduction from Baseline in the Monthly Itch score at Week 24.
    • Change from baseline in Patient's Global Impression of Severity (PGIS) over 24 weeks
    • PGI-C over 24 weeks Change from baseline in ALP at Week 24
    • Change from baseline in bilirubin at Week 24
    • Clinical assessments including, but not limited to:
    • Adverse Events (AEs) and Serious Adverse Events (SAEs)
    • Vital signs
    • 12-lead Electrocardiogram (ECG)
    • Clinical laboratory evaluation (including liver chemistry panel and fasting lipids)
    •Variazione rispetto al basale nel punteggio medio del peggior prurito quotidiano alla Settimana 2
    •Variazione rispetto al basale nel punteggio del sonno mensile misurato con una NRS 0-10 nel corso di 24 settimane
    •Variazione rispetto al basale nei punteggi di dominio del PBC-40 alla Settimana 24
    •Pazienti responder definiti come i pazienti che ottengono una riduzione del punteggio =2 punti rispetto al basale nel punteggio del prurito mensile alla Settimana 24
    •Pazienti responder definiti come i pazienti che ottengono una riduzione =3 punti rispetto al basale nel punteggio del prurito mensile alla Settimana 24
    •Pazienti responder definiti come i pazienti che ottengono una riduzione =4 punti rispetto al basale nel punteggio del prurito mensile alla Settimana 24
    •Variazione rispetto al basale nel PGI-S nel corso di 24 settimane
    •PGI-C nel corso di 24 settimane
    •Variazione rispetto al basale della bilirubina alla Settimana 24
    •Valutazioni cliniche comprese, a titolo esemplificativo ma non esaustivo:
    oEventi avversi (Adverse Event - AE) ed eventi avversi seri (Serious Adverse Event – SAE)
    o Segni vitali
    o Elettrocardiogramma (ECG) a 12 derivazioni
    o Valutazione di laboratorio clinico (compresi pannello di chimica epatica e lipidi a digiuno)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Sleep data will be collected daily from Screening through Week 32. PBC- 40, PGI-S, PGI-C, and lab parameters (ALP, bilirubin) will be collected at
    monthly clinic visits
    I dati sul sonno saranno raccolti giornalmente dallo Screening fino alla Settimana 32. PBC-40, PGI-S, PGI-C e parametri di laboratorio (ALP, bilirubina) saranno raccolti a visite cliniche mensili
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled 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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    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
    Canada
    China
    Japan
    Mexico
    Russian Federation
    United States
    Belgium
    France
    Germany
    Italy
    Netherlands
    Poland
    United Kingdom
    Argentina
    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
    LSLV of the last participant in the study in the trial globally. A participant is considered to have completed the study if he/she has completed all phases of the study including the last visit. For participants that will enroll into a follow on study this last visit is Week 32. If the participant will not enrolled in a follow-on study, this would include completion of the follow-up phone call as shown in the SoA (Section 1.3) of protocol
    LVLS dell'ultimo partecipante dello studio a livello globale. Un partecipante ha completato lo studio se ha completato tutte le fasi del studio inclusa l'ultima visita. Per i partecipanti che verranno inseriti in uno studio di Follow-on, quest'ultima visita corrisponde alla visita della settimana 32. Se il partecipante non verrà arruolato in uno studio di Follow-on, lo studio si considera completato con la telefonata di follow-up come mostrato nella SoA (Sezione 1.3) del protocollo
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months9
    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 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 175
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 55
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 47
    F.4.2.2In the whole clinical trial 230
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Participants who complete treatment in Part A and Part B will be offered the opportunity to take part in a separate long-term follow-on study, where linerixibat will be provided in an open-label manner. Participants who do not enter the follow-on study will have a follow up phone call approximately 7-14 days after the last dose of study drug.
    Ai partecipanti che completano il trattamento nella Parte A e nella Parte B verrà offerta l'opportunità di partecipare a uno studio di Follow-on separato a lungo termine, in cui linerixibat sarà fornito in aperto. I partecipanti che non entrano nello studio di Follow-on riceveranno una telefonata di follow-up circa 7-14 giorni dopo l'ultima somministrazione di farmaco di 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 Decision2021-06-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-06-09
    P. End of Trial
    P.End of Trial StatusOngoing
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