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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43800   clinical trials with a EudraCT protocol, of which   7272   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:2017-003528-62
    Sponsor's Protocol Code Number:EDP305-201
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-05-24
    Trial results View 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 ConcernedSpain - AEMPS
    A.2EudraCT number2017-003528-62
    A.3Full title of the trial
    A Phase 2 Dose Ranging, Randomized, Double Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects with Primary Biliary Cholangitis (PBC) with or without an Inadequate Response to Ursodeoxycholic Acid (UDCA).
    Estudio en fase II, aleatorizado, doble ciego, controlado con placebo y de intervalo de dosis para evaluar la seguridad, tolerabilidad, farmacocinética y eficacia de EDP-305 en pacientes con colangitis biliar primaria (CBP) con o sin respuesta insuficiente al ácido ursodesoxicólico (AUDC)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2 clinical study evaluating safety and efficacy of EDP-305 in Subjects with Primary Biliary Cholangitis (PBC) without adequate response or intolerance to Ursodeoxycholic Acid (UDCA).
    Un estudio clínico de fase 2 para evaluar la seguridad y la eficacia de EDP-305 en sujetos con clangitis biliar primaria (CBP) con respuesta inadecuada o intolerancia al ácido ursodesoxicólico (UDCA).
    A.3.2Name or abbreviated title of the trial where available
    INTREPID
    A.4.1Sponsor's protocol code numberEDP305-201
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03394924
    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 SponsorEnanta Pharmaceuticals, 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 supportEnanta Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationEnanta Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointNathalie Adda
    B.5.3 Address:
    B.5.3.1Street Address500 Arsenal St.
    B.5.3.2Town/ cityWatertown
    B.5.3.3Post codeMA 02472
    B.5.3.4CountryUnited States
    B.5.4Telephone number+16176070705
    B.5.6E-mailnadda@enanta.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 nameEDP-305
    D.3.2Product code EDP-305
    D.3.4Pharmaceutical form 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 INNEDP-305
    D.3.9.1CAS number 1933507-63-1
    D.3.9.2Current sponsor codeEDP-305
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameEDP-305
    D.3.2Product code EDP-305
    D.3.4Pharmaceutical form 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 INNEDP-305
    D.3.9.1CAS number 1933507-63-1
    D.3.9.2Current sponsor codeEDP-305
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    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 placeboTablet
    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
    Primary Biliary Cholangitis (PBC)
    Colangitis biliar primaria (CBP)
    E.1.1.1Medical condition in easily understood language
    A chronic disease in which the small bile ducts in the liver become injured and inflamed and are eventually destroyed. When there are no bile ducts, bile builds up and causes liver damage.
    Enfermedad crónica en la que los conductos biliares pequeños en el hígado se dañan y se inflaman y pueden ser destruidos. Cuando no hay conductos biliares, los fluidos biliares causan daño hepático
    E.1.1.2Therapeutic area Body processes [G] - Immune system processes [G12]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10036680
    E.1.2Term Primary biliary cirrhosis
    E.1.2System Organ Class 100000004871
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the effect of EDP-305 on alkaline phosphatase (ALP) levels.
    Evaluar el efecto de EDP-305 sobre los niveles de fosfatasa alcalina (ALP)
    E.2.2Secondary objectives of the trial
    • To evaluate the safety and tolerability of EDP-305
    • To evaluate the effect of EDP-305 on bilirubin levels
    • To evaluate the effects of EDP-305 on other markers of liver function
    • To evaluate the effects of EDP-305 on non-invasive markers of liver fibrosis
    • To evaluate the effects of EDP-305 on inflammatory markers
    • To evaluate the effects of EDP-305 on lipids
    • To evaluate the effects of EDP-305 on pruritus
    • To evaluate the effects of EDP-305 on Quality of Life (QoL)
    • To evaluate the pharmacokinetics (PK) of EDP-305 and metabolites in plasma
    • To evaluate the pharmacodynamics (PD) of EDP-305
    • Evaluar la seguridad y tolerabilidad de EDP-305.
    • Evaluar el efecto de EDP-305 en la concentración de bilirrubina.
    • Evaluar los efectos de EDP-305 en otros marcadores de la función hepática.
    • Evaluar los efectos de EDP-305 en marcadores no invasivos de fibrosis hepática.
    • Evaluar los efectos de EDP-305 en los marcadores inflamatorios.
    • Evaluar los efectos de EDP-305 en los lípidos.
    • Evaluar los efectos de EDP-305 en el prurito.
    • Evaluar los efectos de EDP-305 en la calidad de vida (CdV).
    • Evaluar la farmacocinética (FC) de EDP-305 y sus metabolitos en el plasma.
    • Evaluar la farmacodinámica (FD) de EDP-305.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    PK/PD substudy
    Additional samples will be collected from subjects at a subset of sites that have the technical capability to collect and process intensive (longer duration) PK samples. At Day 1 and Day 84 (Week 12) PK samples will be collected at predose and 2, 6, and 8 hours postdose. On scheduled visits on Week 2, 4 and 8, PK samples will be collected at three timepoints: predose and at two timepoints postdose; the first samples collected 1 to 3 hours postdose and the second postdose samples collected at least 1 hour later. Where possible, the samples at each visit should be obtained at different times postdose relative to each other.
    Subestudio de farmacocinética y farmacodinámica:
    Se recogerán muestras adicionales a un subconjunto de centros con capacidad técnica para recoger y procesar muestras de farmacocinética intensivas (larga duración). Se recogerán muestras para farmacocinética antes de la dosis en el día 1 y día 84 (semana 12) y 2, 6 y 8 horas después de la dosis. En las visitas programadas de las semanas 2, 4 y 8 las muestras para farmacocinética se recogerán en tres momentos: antes de la dosis y en dos ocasiones tras la misma; las primeras muestras recogidas entre 1 y 3 horas tras la dosis y las segundas muestras al menos 1 hora después de la dosis. Cuando sea posible se obtendrán las muestras en cada visita en distintos momentos tras la dosis en relación a las otras.
    E.3Principal inclusion criteria
    1. An informed consent document must be signed and dated by the subject
    2. Male and female subjects of any ethnic origin between the ages of 18 and 75 years, inclusive
    3. Male or female with a diagnosis of PBC by at least two of the following criteria:
    • History of ALP above ULN for at least 6 months
    • Positive Anti-Mitochondrial Antibodies (AMA) titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay [ELISA] or positive PBC-specific antinuclear antibodies [PBC- ANAb])
    • Documented liver biopsy result consistent with PBC (with no cirrhosis)
    4. For subjects with no documented liver biopsy performed within 2 years, subjects must undergo a transient elastography (Fibroscan) showing liver stiffness <14.0 kPA
    5. Must be on a stable dose of UDCA12-20 mg/kg/day for at least 6 months prior to Screening or intolerant of UDCA in the opinion of the Investigator (no UDCA for at least 12 weeks prior to Screening)
    6. Alkaline Phosphatase (ALP) ≥1.67 × ULN and/or total bilirubin >ULN but <2 × ULN (<2.4 mg/dL)
    7. Subjects must have Screening laboratory values for Hepatitis B surface antigen (HBsAg), anti-HCV antibodies and HCV RNA negative, and Human Immunodeficiency Virus (HIV) 1 and 2 antibodies (Ab) as seronegative. NOTE: Subjects previously infected by chronic hepatitis C and treated with direct acting antivirals (DAAs) with sustained virologic response (SVR) for at least 3 years will be allowed.
    8. Female subjects of childbearing potential must agree to use two effective methods of contraception from the date of Screening until 90 days after the last dose of EDP-305. Effective methods of contraception are defined as:
    • a condom for the male partner and at least one of the following for the female participant:
    o Intrauterine device
    o Oral, injectable, implantable, transdermal, or intravaginal hormonal contraceptive
    Note: The above does not apply to female subjects of non-childbearing potential (ie, physiologically incapable of becoming pregnant) defined as:
    - has had a complete hysterectomy greater than or equal to 3 months prior to dosing or
    - has had a bilateral oophorectomy (ovariectomy) or
    - has had a bilateral tubal ligation or fallopian tube inserts or
    - is postmenopausal (a demonstration of a total cessation of menses for ≥1 year with an FSH level of >35 mIU/mL).
    9. All male participants who have not had a vasectomy must use effective contraception from Day -1 to 90 days after their last dose of study drug. Effective contraception is defined as a condom and spermicide for the male, or condom and at least one of the following for a female partner:
    • Intrauterine device
    • Oral, injectable, implantable, transdermal, or intravaginal hormonal contraceptive
    • Be of non-childbearing potential
    10. Male subjects must agree to refrain from sperm donation from the date of Screening until 90 days after their last dose of study drug
    11. Screening body mass index (BMI) of ≥18 kg/m2
    12. Subject must be willing and able to adhere to the assessments, visit schedule, prohibitions and restrictions, as described in this protocol
    1. El paciente debe firmar y fechar el formulario de consentimiento informado.
    2. Pacientes de ambos sexos y cualquier origen étnico de 18 a 75 años, ambos inclusive.
    3. Pacientes de ambos sexos con diagnóstico de CBP con al menos dos de los criterios siguientes:
    • Antecedentes de FA superior al LSN durante un periodo mínimo de 6 meses.
    • Valores positivos de anticuerpos antimitocondriales (AAM) (>1/40 mediante inmunofluorescencia, positivo para M2 mediante enzimoinmunoanálisis de adsorción [ELISA] o positivo para anticuerpos antinucleares específicos de la CBP [AAN-CBP]).
    • Resultado de biopsia hepática documentada compatible con CBP (sin cirrosis).
    4. Los pacientes sin biopsia hepática documentada realizada en los 2 años anteriores se someterán a una elastografía de transición (Fibroscan) que muestre un resultado de rigidez hepática <14,0 kPA.
    5. Los pacientes deben haber estado recibiendo una dosis estable de AUDC de 12-20 mg/kg/día como mínimo durante los 6 meses anteriores a la selección o ser intolerantes al AUDC a juicio del investigador (el paciente no recibió AUDC por lo menos durante las 12 semanas anteriores a la selección).
    6. Fosfatasa alcalina (ALP) ≥1,67 × LSN y/o bilirrubina total >LSN pero <2 × LSN (<2,4 mg/dl).
    7. Los pacientes deben ser seronegativos en los parámetros analíticos de selección del antígeno de superficie de la hepatitis B (HBsAg), anticuerpos anti-VHC y VHC ARN negativo, y los anticuerpos (Ac) 1 y 2 del virus de la inmunodeficiencia humana (VIH). NOTA: se permitirá la participación de los pacientes infectados anteriormente por el virus de la hepatitis C crónica tratados con antivíricos de acción directa (AAD) y con respuesta virológica sostenida (RVS) durante un mínimo de 3 años.
    8. Mujeres sin capacidad de concebir. La ausencia de capacidad para concebir (esto es, la incapacidad fisiológica para quedarse embarazada) se define por cumplir alguno de los requisitos siguientes:
    • Haberse sometido a una histerectomía completa como mínimo en los 3 meses antes a la administración o
    • haberse sometido a una ovariectomía bilateral o
    • haberse sometido a una ligadura de trompas bilateral o inserciones en las trompas de Falopio o
    • estar en estado posmenopáusico (demostrar el cese total de la menstruación durante ≥1 año con un nivel de FSH >35 mUI/ml).
    9. Todos los participantes que no se hayan sometido a una vasectomía deberán utilizar métodos anticonceptivos eficaces desde el día -1 hasta el día 90 después de la última dosis del fármaco del estudio. Los métodos anticonceptivos eficaces se definen como un preservativo más espermicida para los hombres o bien un preservativo y el uso de uno de los métodos siguientes por parte de la pareja del sexo femenino:
    • Dispositivo intrauterino
    • Anticonceptivo hormonal oral, inyectable, implantable, transdérmico o intravaginal
    • No tener capacidad para concebir
    10. Los hombres deben abstenerse de donar semen desde la fecha de la selección hasta 90 días después de la última dosis del fármaco del estudio.
    11. Índice de masa corporal (IMC) en la selección ≥18 kg/m2.
    12. Voluntad y capacidad de los pacientes para cumplir con las evaluaciones, el calendario de visitas y las prohibiciones y restricciones según lo descrito en el protocolo.
    E.4Principal exclusion criteria
    1. Laboratory Screening Results:
    • AST >5 × ULN
    • ALT >5 × ULN
    • Patients with Gilbert’s syndrome will not be allowed due to interpretability of bilirubin levels
    • Total white blood cells (WBC) <3000 cells/mm3
    • Absolute neutrophil count (ANC) <1500 cells/mm3
    • Platelet count <140,000/mm3
    • Prothrombin time (international normalized ratio, INR) >1.2
    • Serum creatinine >2 mg/dL or creatinine clearance <60 mL/min (based on Cockroft-Gault Method)
    2. Suspected to have relevant nonalcoholic fatty liver disease (NAFLD) as based on the judgment of the Investigator at Screening
    3. Known history of alpha-1-Antitrypsin deficiency
    4. Use of immunosuppressants known to have an effect on the liver of patients with PBC (eg, colchicine, methotrexate, or azathioprine) in the 3 months preceding Screening.
    5. Current use of fibrates, including fenofibrates. NOTE: Subjects who discontinued fibrates for at least 3 months before Screening can participate
    6. Use of an experimental treatment for PBC within the past 6 months
    7. Prior use and/or concomitant treatment with obeticholic acid (OCA)
    8. Use of experimental or unapproved drugs within 1 year of Screening
    9. Any other condition(s) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the Principal Investigator (PI)
    10. Pregnant or nursing females
    11. Recipients of liver or other organ transplantation or anticipated need for orthotropic organ transplantation in one year as determined by a Model for End-Stage Liver Disease (MELD) Score ≥15
    12. Co-existing liver or biliary diseases, such as primary sclerosing cholangitis, choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis (NASH), acute infection of bile duct system or gall bladder, history of gastrointestinal bleeding (secondary to portal hypertension), cirrhosis, cholangiocarcinoma diagnosed or suspected liver cancers
    13. Cirrhosis with or without complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma
    14. Hepatorenal syndrome (type I or II) or Screening serum creatinine >2 mg/dL (178 μmol/L)
    15. Prior variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class A, B and C, esophageal varices, or refractory ascites within the previous 6 months of Screening (defined as date informed consent signed)
    16. Patients with a history of severe pruritus requiring current or prior systemic treatment (e.g., with BAS or rifampicin)
    17. Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease)
    18. Any condition possibly affecting drug absorption (eg, gastrectomy <3 years prior to Screening. NOTE: Subjects who have undergone gastric surgeries known to not affect drug absorption such as gastric band or gastric sleeve will be allowed if they are stable for at least 1 year prior to Screening.
    19. History of regular alcohol consumption exceeding 14 drinks/week for females and 21 drinks/week for males within 6 months of Screening. One drink is defined as 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor)
    20. Participation in a clinical trial within 30 days prior to study drug administration
    21. Clinically significant electrocardiogram (ECG) abnormalities or QTcF greater than 450 ms for males and 470 ms for females at either Screening or Baseline, or any prior history of QT abnormality
    22. Use of CYP3A4 and P-gp inducers and inhibitors within 14 days prior to the first dose of study medication and throughout study duration
    23. Clinically significant history of drug sensitivity or allergy, as determined by the PI
    24. Subject has received an investigational agent or investigational vaccine within 30 days, or a biological product within 3 months or 5 elimination half-lives (whichever is longer) prior to the planned intake of study drug
    25. Use of a new statin regimen from Screening and throughout study duration.
    NOTE: Subjects on a stable dose of statins for at least 3 months prior to Screening are allowed. No dose modification during the study will be allowed.
    26. Use of immunosuppressants (eg, systemic corticosteroids) for more than 2 consecutive weeks in duration within 1 year prior to Screening.
    1.Resultados de los análisis en la selección:
    •AST >5 × LSN.
    •ALT >5 × LSN.
    •No se permitirá la participación de los pacientes con síndrome de Gilbert a causa de la interpretabilidad de los niveles de bilirrubina.
    •Recuento total de leucocitos (LEU) <3000 células/mm3.
    •Recuento absoluto de neutrófilos (RAN) <1500 células/mm3.
    •Recuento de trombocitos <140 000/mm3.
    •Índice internacional normalizado (INR) del tiempo de protrombina >1,2.
    •Creatinina sérica >2 mg/dl o aclaramiento de creatinina <60 ml/min (según la fórmula de Cockroft-Gault).
    2.Sospecha de enfermedad hepática grasa no alcohólica (EHGNA) de interés a juicio del investigador en la selección.
    3.Antecedentes conocidos de deficiencia de alfa-1-antitripsina.
    4.Uso de fármacos inmunodepresores que se sabe afectan al hígado en pacientes con CBP en los 3 meses anteriores a la selección.
    5.Uso actual de fibratos, incluyendo fenofibratos. NOTA: los pacientes que hayan dejado los fibratos como mínimo 3 meses antes de la selección pueden participar.
    6.Uso de algún tratamiento experimental para tratar la CBP en los últimos 6 meses.
    7.Uso anterior y/o tratamiento concomitante con ácido obeticólico (AOC).
    8.Uso de fármacos experimentales o sin autorizar en el año anterior a la selección.
    9.Otras afecciones que pudieran poner en peligro la seguridad del paciente o poner en peligro la calidad del estudio clínico a juicio del investigador principal (IP).
    10.Mujeres embarazadas o que estén en periodo de lactancia.
    11.Receptores de un trasplante de hígado o de otros órganos o necesidad prevista de un trasplante de órganos ortotrópico en el plazo de un año según lo determinado por una puntuación ≥15 del modelo de hepatopatía en estadio terminal (MELD).
    12.Enfermedades hepáticas o biliares coexistentes tales como colangitis esclerosante primaria, coledocolitiasis, hepatitis aguda o crónica, hepatitis autoinmunitaria, hepatopatía alcohólica, esteatohepatitis no alcohólica (EHNA), infección aguda de las vías biliares o la vesícula biliar, antecedentes de hemorragia gastrointestinal (secundaria a hipertensión portal), cirrosis, colangiocarcinoma diagnosticado o sospecha de cáncer hepático.
    13.Cirrosis con o sin complicaciones, incluyendo antecedentes o presencia de: peritonitis bacteriana espontánea, carcinoma hepatocelular.
    14.Síndrome hepatorrenal (tipo I o II) o creatinina sérica en la selección >2 mg/dl (178 μmol/l.)
    15.Hemorragia digestiva por rotura de varices esofágicas anterior, encefalopatía no controlada, Child-Pugh clase B y C, varices esofágicas o ascitis refractaria en los 6 meses previos a la selección (definida como la fecha en que se firmó el consentimiento informado).
    16.Pacientes con antecedentes de prurito intenso que requiere tratamiento sistémico (p. ej., con secuestrantes de ácidos biliares [BAS] o rifampicina) en la actualidad o anteriormente.
    17.Enfermedades que provoquen el aumento de la FA (p. ej., enfermedad de Paget).
    18.Cualquier afección con posibilidad de afectar a la absorción del fármaco (p. ej., gastrectomía <3 años antes de la selección). NOTA: se permitirá la participación de los pacientes que se hayan sometido a una cirugía gástrica que se sabe afecta a la absorción de medicamentos, tal como la gastroplastia con banda ajustable o gastrectomía tubular, si se encuentran estables durante un mínimo de 1 año antes de la selección.
    19.Antecedentes de consumo habitual de alcohol que supere las 14 bebidas/semana en las mujeres y las 21 bebidas/semana en los hombres en los 6 meses anteriores a la selección. Una bebida se define como 150 ml (5 onzas) de vino, 360 ml (12 onzas) de cerveza o 45 ml (1,5 onzas) de bebidas de alta graduación).
    20.Participación en un ensayo clínico en los 30 días anteriores a la administración del fármaco del estudio.
    21.Anomalías en el electrocardiograma (ECG) de importancia clínica o QTcF superior a 450 ms en hombres y 470 ms en mujeres en la selección o el inicio del estudio, o antecedentes de anomalías del segmento QT.
    22.Uso de inductores o inhibidores de CYP3A4 y P-gp en los 14 días anteriores a la primera dosis del medicamento del estudio y durante todo el estudio.
    23.Antecedentes de importancia clínica de sensibilidades o alergias farmacológicas según lo determinado por el IP.
    24.El paciente ha recibido un fármaco o vacuna en investigación en los 30 días anteriores o un producto biológico en los 3 meses o 5 semividas de eliminación (el periodo que sea más largo) anteriores a la toma prevista del fármaco del estudio.
    25.Uso de un régimen de estatinas nuevo desde la selección y durante el periodo del estudio. NOTA: se permitirá la participación de los pacientes en tratamiento con una dosis estable de estatinas durante un mínimo de 3 meses antes de la selección. No se permitirá la modificación de la dosis durante el estudio.
    26.Uso de fármacos inmunodepresores (p. ej., corticoesteroides sistémicos) durante más de 2 semanas consecutivas en el año previo a la selección.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of subjects with at least 20% reduction in ALP from pretreatment value or normalization of ALP at Week 12
    Proporción de sujetos con al menos un 20% de reducción en ALP desde el valor del pretratamiento o normalización de la ALP en la semana 12.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 12
    Semana 12
    E.5.2Secondary end point(s)
    • Frequency of adverse events (AEs), serious AEs, and AEs leading to discontinuation through Week 12
    • Bilirubin (Total, Conjugated, Unconjugated) decline from Baseline at Week 12
    • Change from Baseline in Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST), Gamma-Glutamyl transferase (GGT) at Week 12
    • Change from Baseline of noninvasive liver fibrosis markers (Enhanced Liver Fibrosis [ELF] panel, PRO C3, AST to Platelet Ratio Index [APRI] and fibrosis-4 [FIB-4]) at Week 12
    • Change from Baseline in fibrinogen, CRP, IL6, IL1β, TNF-α, TNF-β , alpha2 macroglobulin and haptoglobin levels at Week 12
    • Change from Baseline in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
    • Change from Baseline in 5D-itch scale and Visual Analog Score (VAS) at Week 12
    • Change from Baseline in PBC-40 Quality of Life (QoL) at Week 12
    • Pharmacokinetic parameters of EDP-305 (and metabolites): Cmax, Tmax, and AUClast.
    • Pharmacodynamic parameters of EDP-305: FGF19, C4 and Bile Acid (BA) at Week 12
    • Frecuencia de acontecimientos adversos (AA), AA graves y AA que dan lugar a la interrupción del tratamiento hasta la semana 12.
    • Disminución de la bilirrubina (total, conjugada, no conjugada) con respecto al inicio en la semana 12.
    • Variación con respecto al inicio en las concentraciones de alanina aminotransferasa (ALT), aspartato aminotransferasa (AST) y gamma-glutamil transferasa (GGT) en la semana 12.
    • Variación con respecto al inicio en los marcadores no invasivos de la fibrosis hepática (puntuación de la prueba de fibrosis hepática mejorada [ELF®], PRO C3, índice del cociente AST/plaquetas [APRI] y fibrosis-4 [FIB-4]) en la semana 12.
    • Variación con respecto al inicio en la concentración de fibrinógeno, PCR-as, IL6, IL1β, TNF-α, TNF-β, alfa2 macroglobulina y haptoglobina en la semana 12.
    • Variación con respecto al inicio en la concentración de triglicéridos (TG), colesterol total (CT), colesterol unido a lipoproteínas de alta densidad (HDL-C) y colesterol unido a lipoproteínas de baja densidad (LDL-C) en la semana 12.
    • Variación con respecto al inicio en la escala 5D de prurito y la escala visual analógica (EVA) en la semana 12.
    • Cambio con respecto al inicio en la calidad de vida (CdV) PBC-40 en la semana 12.
    • Parámetros farmacocinéticos de EDP-305 (y sus metabolitos): Cmáx, Tmáx y ABCúlt.
    • Parámetros farmacodinámicos de EDP-305: FGF19, C4 y ácido biliar (AB) en la semana 12.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 12
    Semana 12
    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 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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned 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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA40
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Austria
    Belgium
    Canada
    France
    Germany
    Netherlands
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Last patient last visit.
    Última visita del último paciente.
    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 months5
    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 months5
    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: 100
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 19
    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 state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 119
    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)
    Since the IP (EDP 305) is in early phase of the development program, there is currently no plans for continuing treatment with EDP-305 following completion of this study.
    Subjects will continue with the standard of care or alternative medication as per discretion of the investigator or primary health care provider.
    Dado que el MI (EDP-305) se encuentra en una fase temprana de desarrollo, actualmente no hay planes para continuar el tratamiento con EDP-305 tras la finalización de este estudio.
    Los sujetos continuarán con el tratamiento habitual o medicación alternativa según decisión del investigador o el médico habitual.
    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 Decision2018-08-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-07-31
    P. End of Trial
    P.End of Trial StatusCompleted
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA