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   43843   clinical trials with a EudraCT protocol, of which   7282   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:2016-000821-37
    Sponsor's Protocol Code Number:GS-US-416-2124
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-09-30
    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 ConcernedUK - MHRA
    A.2EudraCT number2016-000821-37
    A.3Full title of the trial
    A Phase 2, Double-Blind, Randomized Study Evaluating the Safety, Tolerability, and Efficacy of GS-4997 in Combination with Prednisolone versus Prednisolone Alone in Subjects with Severe Alcoholic Hepatitis (AH)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Clinical trial to evaluate safety, and effectiveness of GS-4997 in combination with an existing therapy (prednisolone) vs prednisolone alone in subjects with Severe Alcoholic Hepatitis
    A.4.1Sponsor's protocol code numberGS-US-416-2124
    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 SponsorGilead Sciences, 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 supportGilead Sciences, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGilead Sciences International Ltd.
    B.5.2Functional name of contact pointClinical Trials Mailbox
    B.5.3 Address:
    B.5.3.1Street AddressFlowers Building, Granta Park
    B.5.3.2Town/ cityAbington, Cambridge
    B.5.3.3Post codeCB21 6GT
    B.5.3.4CountryUnited Kingdom
    B.5.5Fax number+441223897284
    B.5.6E-mailclinical.trials@gilead.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.3.2Product code GS-4997
    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 INNGS-4997
    D.3.9.1CAS number 1448428-04-3
    D.3.9.2Current sponsor codeGS-4997
    D.3.9.3Other descriptive nameGS-4997
    D.3.9.4EV Substance CodeSUB167748
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number18
    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 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
    Alcoholic Hepatitis
    E.1.1.1Medical condition in easily understood language
    Inflammation of the liver due to excessive alcohol intake
    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 19.0
    E.1.2Level LLT
    E.1.2Classification code 10001624
    E.1.2Term Alcoholic hepatitis
    E.1.2System Organ Class 100000004871
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is as follows: To evaluate the safety and tolerability of GS-4997 in combination with prednisolone versus prednisolone alone in subjects with severe AH.
    E.2.2Secondary objectives of the trial
    The secondary objectives of this study are as follows:
    -To assess changes in hepatic synthetic function [liver biochemistry, Model for End-Stage Liver Disease [MELD] score, Child-Pugh score, the Lille model, Maddrey’s Discriminant Function (Maddrey’s DF), and the HepQuantTM test (optional sub-study, select sites only)];
    To assess mortality at 28 days, 12 weeks and 24 weeks;
    -To determine the incidence of liver transplantation;
    -To determine the incidence of hepatorenal syndrome (HRS);
    -To determine the incidence of infection;
    -To assess length of hospital stay.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Intensive PK Substudy
    Subjects may choose to participate in an optional PK substudy. The PK substudy will be performed at one visit, at any time between Weeks 1 and 3 (inclusive). Blood samples will be drawn predose and at 0.5, 1, 2, 4, 6, 8, and 24 hours postdose.

    HepQuantTM Sub-Study (for US sites only)
    The HepQuant™ test is an investigational test which assesses hepatic portal circulation and other measures of liver function using a combination of blood testing and non-radioactive isotopes. Results from the HepQuant™ testing will be correlated to clinical outcomes to advance the development of this non-invasive testing methodology. Participating US sites will be selected by Gilead Sciences. Subjects will have to sign a separate informed consent form prior to participation in this substudy. All subjects who enroll at the participating US sites will be eligible to enroll in this substudy, but participation will be optional. Each participant will undergo HepQuant™ testing at baseline/Day 1, Weeks 1, 4, 12, and 24.
    E.3Principal inclusion criteria
    1) Males and non-pregnant, non-lactating females between 18-70 years of age, inclusive based on the date of the screening visit;
    2) Willing and able to give informed consent prior to any study specific procedures being performed. In subjects with hepatic encephalopathy (HE), which may impair decision-making, consent will be obtained per hospital procedures (eg, by legal Authorized Representative);
    3) Clinical diagnosis of severe AH
    4) All female subjects of childbearing potential must agree to use a highly effective method of contraception during intercourse from the screening visit throughout the study period and for 90 days following the last dose of study drug. If females utilize hormonal agents as one of their contraceptive methods, the same hormonal methods must have been used for at least 3 months before study dosing. Females on hormonal methods must also utilize a barrier method as another form of contraception;
    5) Male subjects must refrain from sperm donation from screening through at least 90 days following the last dose of study drug;
    6) Male subjects must agree to use condoms during intercourse from screening through study completion and for 90 days following the last dose of study drug;
    7) Female subjects must refrain from egg donation or harvest for 90 days after last dose of study drug;
    8) Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions
    E.4Principal exclusion criteria
    1) Pregnant or lactating females;
    2) Other causes of liver disease including chronic hepatitis B (hepatitis B surface antigen [HBsAg] positive), chronic hepatitis C (HCV RNA positive), acetaminophen hepatotoxicity, biliary obstruction, and autoimmune liver disease;
    3) Serum AST >400 U/L or ALT >300 U/L;
    4) MELD >30 at screening;
    5) Maddrey’s DF >60 at screening;
    6) Grade 4 Hepatic Encephalopathy (HE) by West Haven criteria;
    7) Concomitant or previous history of hepatocellular carcinoma;
    8) History of liver transplantation;
    9) HIV Ab positive;
    10) Uncontrolled sepsis;
    11) Uncontrolled gastrointestinal (GI) bleeding or controlled GI bleeding within 7 days of screening that was associated with shock or required transfusion of more than 3 units of blood;
    12) Type 1 hepatorenal syndrome (HRS) or renal failure defined as a serum creatinine >221 μmol/L (> 2.5 mg/dL) or the requirement for renal replacement therapy;
    13) Subjects dependent on inotropic (eg, epinephrine or norepinephrine) or ventilatory support (ie, endotracheal intubation or positive-pressure ventilation);
    14) Portal vein thrombosis;
    15) Acute pancreatitis;
    16) Cessation of alcohol consumption for more than 2 months before baseline/Day 1;
    17) Severe associated disease (eg, cardiac failure, acute myocardial infarction, severe cardiac arrhythmias, severe pulmonary disease, neurologic disease,) that may lead to premature mortality within the study period;
    18) Malignancy within the 2 years prior to screening, with the exception of specific cancers that have been cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible.
    19) Positive urine screen for amphetamines, cocaine or opiates (ie, heroin, morphine) at screening. Subjects on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to screening may be included in the study. Subjects with positive cannabis drug screen may be included in the study. Subjects with a positive urine drug screen due to prescription opioid-based medication are eligible if the prescription and diagnosis are reviewed and approved by the investigator;
    20) Treatment with immunosuppressive drugs [eg, systemic corticosteroids (inhaled and topical steroids are allowed), budesonide, tacrolimus, sirolimus, cyclosporine, azathioprine, mycophenolate mofetil, and methotrexate], pentoxifylline, or N-acetylcysteine (NAC) within 6 month of screening;
    21) Use of the following CYP3A4 inhibitors (clarithromycin, conivaptan, grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, bupenorphine/naloxone, telithromycin, voriconazole) or CYP3A4 inducers (carbamazepine, phenytoin, rifampin, St. John’s Wort) within 2 weeks of baseline;
    22) Active ocular herpes simplex;
    23) Any laboratory abnormality or condition that, in the investigator’s opinion, could adversely affect the safety of the subject or impair the assessment of study results;
    24) Participation in another investigational study of a drug or device within 1 month prior or within 5 half-lives of the prior investigational agent (whichever is longer) prior to screening;
    25) Concurrent participation in another therapeutic clinical study;
    26) Known hypersensitivity to the study drugs (GS-4997 and prednisolone), the metabolites, or formulation excipient;
    27) Presence of any condition that could, in the opinion of the investigator, compromise the subject’s ability to participate in the study, such as history of substance abuse other than alcohol use or a psychiatric or medical condition;
    28) Unavailable for follow-up assessment or concern for subject’s compliance with the protocol procedures
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the safety of GS-4997 in combination with prednisolone versus prednisolone alone in subjects with severe AH.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Study visits will occur at baseline/Day 1 and on Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24.
    E.5.2Secondary end point(s)
    Clinical outcomes:
    -Mortality at 28 days, 12 weeks, and 24 weeks
    -HRS
    -Infection
    -Length of hospital stay
    -Liver transplantation
    -Measures of hepatic synthetic function
    E.5.2.1Timepoint(s) of evaluation of this end point
    Study visits will occur at baseline/Day 1 and on Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24.
    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 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 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 trial2
    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 concerned13
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA39
    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
    Austria
    Belgium
    Canada
    France
    Switzerland
    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 subject’s last observation (or visit).
    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 months1
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months5
    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: 108
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 12
    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
    In subjects with hepatic encephalopathy (HE), which may impair decision-making, consent will be obtained per hospital procedures (eg, by legal Authorized Representative);
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 65
    F.4.2.2In the whole clinical trial 120
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    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 Decision2017-01-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-01-06
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-05-25
    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-Thu Apr 18 08:41:08 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA