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   44202   clinical trials with a EudraCT protocol, of which   7332   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:2019-000204-14
    Sponsor's Protocol Code Number:GS-US-428-4194
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2019-06-27
    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 number2019-000204-14
    A.3Full title of the trial
    A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of Cilofexor in Non-Cirrhotic Subjects with Primary Sclerosing Cholangitis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to assess the safety and efficacy of a new investigational drug in subjects with Primary Sclerosing Cholangitis Without Cirrhosis
    A.4.1Sponsor's protocol code numberGS-US-428-4194
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03890120
    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.5.4Telephone number+441223897300
    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 Yes
    D.2.5.1Orphan drug designation numberEMA/OD/0000002498
    D.3 Description of the IMP
    D.3.1Product nameCilofexor
    D.3.2Product code GS-9674
    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 INNCilofexor
    D.3.9.1CAS number 1418274-28-8
    D.3.9.2Current sponsor codeGS-9674
    D.3.9.3Other descriptive nameGS-9674
    D.3.9.4EV Substance CodeSUB183672
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product 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 Yes
    D.2.5.1Orphan drug designation numberEMA/OD/0000002498
    D.3 Description of the IMP
    D.3.1Product nameCilofexor
    D.3.2Product code GS-9674
    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 INNCilofexor
    D.3.9.1CAS number 1418274-28-8
    D.3.9.2Current sponsor codeGS-6974
    D.3.9.3Other descriptive nameGS-9674
    D.3.9.4EV Substance CodeSUB183672
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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
    D.8 Placebo: 2
    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
    Primary Sclerosing Cholangitis
    E.1.1.1Medical condition in easily understood language
    Primary sclerosing cholangitis is a chronic disease which causes scarring of the bile ducts. This can block the flow of bile which can cause damage to the liver over time.
    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 20.1
    E.1.2Level LLT
    E.1.2Classification code 10036732
    E.1.2Term Primary sclerosing cholangitis
    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 whether cilofexor (CILO, previously known as GS-9674) reduces the risk of fibrosis progression among non-cirrhotic subjects with primary sclerosing cholangitis (PSC)
    E.2.2Secondary objectives of the trial
    -To assess the safety and tolerability of CILO
    -To evaluate changes in serum concentrations of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and bile acids
    -To evaluate whether CILO increases the proportion of subjects with ≥ 25% relative reduction in serum ALP concentration from baseline (biochemical response) and no worsening of fibrosis according to the Ludwig classification (histologic response)
    -To evaluate changes in liver fibrosis including hepatic collagen content, fibrosis stage improvement, progression to cirrhosis, and changes in noninvasive markers of fibrosis, including liver stiffness by FibroScan® and enhanced liver fibrosis test (ELF™ test) score
    -To evaluate changes in health-related quality of life (QoL) based on the disease-specific PSC patient-reported outcome (PSC-PRO)
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Optional Intensive PK and PD Substudy
    All subjects will have the option to participate in the intensive PK and PD substudy. For subjects who agree to participate and provide their consent, the intensive PK and PD sampling will be performed once any time between Week 4 to Week 84 (inclusive).
    E.3Principal inclusion criteria
    1) Diagnosis of large duct PSC based on cholangiogram (magnetic resonance cholangiopancreatography [MRCP], endoscopic retrograde cholangiopancreatography [ERCP], or percutaneous transhepatic cholangiogram [PTC])
    2) Liver biopsy at screening that is deemed acceptable for interpretation and demonstrates stage F0 – F3 fibrosis (according to the Ludwig classification) in the opinion of the central reader
    a. A historical liver biopsy within 6 months of the screening visit may be accepted as the screening biopsy if the sample is deemed acceptable for interpretation by the central reader.
    3) Subject has the following laboratory parameters at the screening visit, as determined by the central laboratory:
    a. Platelet count ≥ 150,000/mm3
    b. Estimated glomerular filtration rate (eGFR) ≥ 30 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation
    c. ALT ≤ 8 x upper limit of normal (ULN)
    d. Total bilirubin < 2 mg/dL, unless the subject is known to have Gilbert’s syndrome or hemolytic anemia
    e. International normalized ratio (INR) ≤ 1.4, unless due to therapeutic anticoagulation
    f. Negative anti-mitochondrial antibody
    4) For subjects on ursodeoxycholic acid (UDCA), the dose of UDCA must have been stable in the opinion of the investigator for at least 6 months before screening. For subjects not on UDCA, no UDCA use for at least 6 months prior to screening.
    E.4Principal exclusion criteria
    1) Current or prior history of any of the following:
    a. Cirrhosis as defined by any of the following:
    i. Liver biopsy demonstrating stage F4 fibrosis according to the Ludwig classification (or equivalent)
    ii. Decompensated liver disease, including ascites, hepatic encephalopathy (HE), or variceal hemorrhage
    iii. Liver stiffness > 20.0 kPa by FibroScan®
    b. Liver transplantation
    c. Cholangiocarcinoma or hepatocellular carcinoma (HCC). If a dominant stricture has been identified, cholangiocarcinoma must be adequately excluded in the opinion of the investigator prior
    to Day 1.
    d. Ascending cholangitis within 30 days of screening
    2) Presence of a percutaneous drain or biliary stent
    3) Other causes of liver disease including immunoglobulin (IgG4)-related sclerosing
    cholangitis, autoimmune hepatitis/PSC overlap syndrome, secondary sclerosing cholangitis, small duct PSC (histologic evidence of PSC with normal bile ducts on cholangiography), and viral, metabolic, alcoholic, and other autoimmune conditions. Subjects with hepatic steatosis may be included if there is no evidence of nonalcoholic steatohepatitis (NASH) on liver biopsy in the opinion of the central reader
    4) Current or prior history of any of the following:
    a. Malignancy within 5 years of screening with the following exceptions:
    i. Adequately treated carcinoma in situ of the cervix
    ii. Adequately treated basal or squamous cell cancer or other localized non-melanoma skin cancer.
    Subjects under evaluation for possible malignancy are not eligible.
    b. Unstable cardiovascular disease as defined by any of the following:
    i. Unstable angina, myocardial infarction, coronary artery bypass graft surgery or coronary angioplasty within 6 months prior to screening
    ii. Transient ischemic attack or cerebrovascular accident within 6 months prior to screening
    iii. Symptomatic obstructive valvular heart disease or hypertrophic cardiomyopathy
    iv. Symptomatic congestive heart failure
    v. Uncontrolled or recurrent ventricular tachycardia or other arrhythmia requiring an automatic implantable cardioverter defibrillator (AICD). Stable, controlled atrial fibrillation is allowed.
    c. Hypercoagulable condition or venous or arterial thromboembolic disease
    d. Intestinal resection or malabsorptive condition that may limit the absorption of CILO. Prior cholecystectomy and appendectomy are permitted.
    5) Child-Pugh (CP) score > 6 at Screening, unless due to an alternative etiology such as Gilbert’s syndrome or therapeutic anticoagulation
    6) Model for End-stage Liver Disease (MELD) score > 12 at Screening, unless due to an alternate etiology such as therapeutic anticoagulation
    7) HIV infection (HIV antibody [Ab] and HIV RNA positive)
    8) Chronic HBV infection (hepatitis B surface antigen [HBsAg] positive)
    9) Chronic HCV infection (HCV Ab and HCV RNA positive). Subjects cured of HCV infection ≥ 2 years prior to screening are eligible.
    10) Current moderate to severe inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn’s disease, and indeterminate colitis) defined as a screening visit Partial Mayo score of > 4 and/or a score in the screening visit Rectal Bleeding domain > 1, unless bleeding is due to perianal disease
    Note: Subjects with IBD who currently have an external ostomy bag are not subject to this exclusion criterion and need not undergo Partial Mayo evaluation at screening
    11) Habitual alcohol consumption greater than 21 oz/week for males or 14 oz/week for females (1 oz/30 mL of alcohol is present in one 12 oz/360 mL beer, one 4 oz/120 mL glass of wine, and a 1 oz/30 mL measure of 40% proof alcohol)
    12) Use of antibiotics (eg, vancomycin, metronidazole, minocycline, etc.) for the treatment of PSC within 60 days of Screening. Antibiotic prophylaxis for ascending cholangitis is permitted if stable in the opinion of the investigator for at least 6 months prior to Screening
    13) Use of any prohibited concomitant medications
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the proportion of subjects with progression of liver fibrosis, as defined by a ≥ 1-stage increase in fibrosis according to the Ludwig classification at Week 96
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline/Day 1 and at Week 96
    E.5.2Secondary end point(s)
    The secondary endpoints of this study are as follows:
    -Changes from baseline in serum concentrations of ALP, GGT, ALT, and bile acids at Week 96
    -The proportion of subjects with ≥ 25% relative reduction in serum ALP concentration from baseline (biochemical response) and no worsening of fibrosis according to the Ludwig classification (histologic response)
    -Changes from baseline in liver fibrosis, including hepatic collagen content, fibrosis improvement, and progression to cirrhosis (according to the Ludwig classification), and noninvasive markers of fibrosis, including liver stiffness by FibroScan® and ELF™ test score, at Week 96
    -Changes from baseline in health-related QoL based on the disease specific PSC-PRO at Week 96
    E.5.2.1Timepoint(s) of evaluation of this end point
    Baseline/Day 1 and at Week 96
    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 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 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 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 concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA80
    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
    Denmark
    France
    Germany
    Israel
    Italy
    Japan
    Netherlands
    New Zealand
    Spain
    Sweden
    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 patient last visit (LPLV)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months10
    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 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: 360
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 160
    F.4.2.2In the whole clinical trial 400
    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 Decision2019-07-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-07-15
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    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