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   43851   clinical trials with a EudraCT protocol, of which   7283   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:2016-004625-16
    Sponsor's Protocol Code Number:GS-US-320-4035
    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:2017-08-16
    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 number2016-004625-16
    A.3Full title of the trial
    A Phase 2, Open-label Study to Evaluate the Safety and Efficacy of Switching to Tenofovir Alafenamide (TAF) from Tenofovir Disoproxil Fumarate (TDF) and/or Other Oral Antiviral Treatment (OAV) in Virologically Suppressed Chronic Hepatitis B Subjects with Renal and/or Hepatic Impairment
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to understand the safety and effectiveness of switching to a new drug called Vemlidy from an existing drug called Viread or other oral antiviral treatments drugs for the treatment of long term hepatitis B infection in subjects with renal and/or hepatic impairment
    A.4.1Sponsor's protocol code numberGS-US-320-4035
    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+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 Yes
    D.2.1.1.1Trade name Vemlidy
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences International Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameVemlidy
    D.3.2Product code J05AF13
    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 INNTENOFOVIR ALAFENAMIDE
    D.3.9.1CAS number 379270-37-8
    D.3.9.4EV Substance CodeSUB121761
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic Hepatitis B
    E.1.1.1Medical condition in easily understood language
    Long term infection with hepatitis B virus
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10008910
    E.1.2Term Chronic hepatitis B
    E.1.2System Organ Class 10021881 - Infections and infestations
    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 objectives of this switch study are as follows:
    -To evaluate the safety and tolerability of TAF 25 mg QD at Week 24
    -To measure the proportion of subjects achieving virologic response (HBV DNA < 20 IU/mL) at Week 24
    E.2.2Secondary objectives of the trial
    -To evaluate the safety and tolerability of TAF 25 mg QD at Weeks 48 and 96
    -To measure the proportion of subjects achieving virologic response (HBV DNA < 20 IU/mL) at Weeks 48 and 96
    -To evaluate biochemical and serological (loss of HBeAg with seroconversion to anti-HBe in HBeAg-positive subjects and loss of HBsAg with seroconversion to anti-HBs) responses at Weeks 24, 48, and 96
    -To evaluate the effect of TAF 25 mg QD on renal parameters at Weeks 24, 48, and 96 in subjects with moderate or severe renal impairment and hepatically impaired subjects
    -To evaluate the safety of TAF 25 mg QD as determined by percentage change from Baseline in hip and spine bone mineral density at Weeks 24, 48, and 96
    -To evaluate the effect of TAF 25 mg QD on fibrosis as assessed by Fibrotest® at Weeks 24, 48, and 96
    -To evaluate the effect of TAF 25 mg QD on changes in Child-Pugh-Turcotte and Model for End-stage Liver Disease scores at Weeks 24, 48, and 96 in hepatically impaired subjects
    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 Pharmacokinetic Substudy (Optional)
    A PK substudy will be performed in a subset of subjects (Part A, Cohort 2 [ESRD subjects on HD at selected study sites, target n = 10 to 15] and Part B subjects [hepatic impairment, target n = 10 to 15]). Separate consent for the PK substudy is required. The substudy will include intensive PK profiling in plasma and serial blood samples will be collected at one of the Week 4, 8, or 12 on-treatment visits (on the day prior to hemodialysis for Part A, Cohort 2 subjects [ESRD subjects on HD]).
    E.3Principal inclusion criteria
    Subjects must meet all of the following inclusion criteria to be eligible to participate in the study:

    All Subjects (Parts A and B):
    1) Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
    2) Adult male or non-pregnant female subjects, ≥ 18 years of age based on the date of the Screening visit. A negative serum pregnancy test at Screening is required for female subjects of childbearing potential
    3) Documented evidence of chronic HBV infection (e.g. HBsAg positive for ≥ 6 months)
    4) Normal ECG (or if abnormal, determined by the Investigator not to be clinically significant)
    5) ALT ≤ 10 × upper limit of normal (ULN) at Screening by central laboratory
    6) Must be willing and able to comply with all study requirements

    Part A Only (renal impairment):
    1) Maintained on TDF and/or other OAV treatment(s) for CHB for at least 48 weeks and with viral suppression (HBV DNA < LLOQ) for ≥ 6 months prior to Screening
    2) Moderate renal impairment (30 mL/min ≤ eGFRCG ≤ 59 mL/min), severe renal impairment (15 mL/min ≤ eGFRCG < 30 mL/min) using the Cockcroft-Gault equation, or ESRD (eGFR < 15 mL/min) maintained on HD

    Part B Only (hepatic impairment):
    1) Maintained on TDF and/or other OAV(s) for CHB for at least 48 weeks and with viral suppression (HBV DNA < LLOQ) for ≥ 6 months prior to Screening
    2) CPT score (Appendix 7) of 7-12 (inclusive) OR a past history of CPT score ≥ 7 and any CPT score ≤ 12 at Screening
    3) eGFRCG ≥ 30 mL/min using the Cockcroft-Gault equation
    E.4Principal exclusion criteria
    All Subjects (Parts A & B):
    1) Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study
    2) Males and females of reproductive potential who are unwilling to use an “effective”, protocol-specified method(s) of contraception during the study
    3) Co-infection with HCV, HIV, or HDV
    -Subjects who are HCV positive, but have a documented negative HCV RNA, are eligible
    4) Prior Interferon (IFN) use within 6 months of Screening
    5) Evidence of hepatocellular carcinoma (i.e. evidenced by imaging within 6 months of Screening)
    6) Received solid organ or bone marrow transplant
    7) Significant cardiovascular, pulmonary, or neurological disease in the opinion of the investigator
    8) Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Subjects under evaluation for possible malignancy are not eligible
    9) Currently receiving therapy with immunomodulators (e.g. corticosteroids), nephrotoxic agents, or agents capable of modifying renal excretion
    10) Known hypersensitivity to study drugs, metabolites, or formulation excipients
    11) Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance
    12) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements.
    13) Use of investigational agents within 3 months of Screening, unless allowed by the Sponsor
    14) Use of any prohibited medication

    Part A Only (renal impairment):
    1) Current or historical evidence of clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage)
    2) Abnormal hematological and biochemical parameters
    3) Subjects with ESRD (i.e. eGFRCG < 15 mL/min) not on HD, or those on other forms of renal replacement therapy (i.e. peritoneal dialysis)

    Part B Only (hepatic impairment):
    1) Active variceal bleeding within 6 months or prior placement of a portosystemic shunt (such as transjugular intrahepatic portosystemic shunt [TIPS])
    2) History of hepatorenal syndrome, hepatopulmonary syndrome, Grade 3 or Grade 4 hepatic encephalopathy, or spontaneous bacterial peritonitis within 6 months of Screening
    3) Grade 2 hepatic encephalopathy at Screening
    4) MELD score ≥ 30
    5) Abnormal hematological and biochemical parameters
    E.5 End points
    E.5.1Primary end point(s)
    -The primary safety endpoint is the incidence of graded adverse events and graded laboratory abnormalities at Week 24.
    -The primary efficacy endpoint is the proportion of subjects achieving virologic response (plasma HBV DNA < 20 IU/mL) at Week 24.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 24
    E.5.2Secondary end point(s)
    The Secondary safety endpoints are:
    -Incidence of graded adverse events and graded laboratory abnormalities at Week 48 and 96
    -Change from baseline in eGFRCG at Weeks 24, 48, and 96 in subjects with moderate or severe renal impairment and hepatically impaired subjects
    -Percent change from baseline in hip and spine bone mineral density (BMD) at Weeks 24, 48, and 96

    The Secondary efficacy endpoints are:
    -Proportion of subjects achieving virologic response (plasma HBV DNA < 20 IU/mL ) at Weeks 48 and 96
    -Proportion of subjects with plasma HBV DNA < 20 IU/mL and target detected/not detected (i.e. < LLOD) at Weeks 24, 48, and 96
    -Proportion of subjects with serological response (loss of HBsAg and seroconversion to anti-HBs, loss of HBeAg and seroconversion to anti-HBe in HBeAg-positive subjects) at Weeks 24, 48, and 96
    -Proportion of subjects with biochemical response (normal ALT and normalized ALT) at Weeks 24, 48, and 96
    -Change in fibrosis as assessed by FibroTest® at Weeks 24, 48, and 96
    -Change from baseline in CPT score (Appendix 7) and MELD score at Weeks 24, 48, and 96 in hepatically impaired subjects
    E.5.2.1Timepoint(s) of evaluation of this end point
    Weeks 24, 48, 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 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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.3Other No
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA8
    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
    Canada
    Hong Kong
    Korea, Republic of
    Taiwan
    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
    The end of the study will be the last subjects’ last observation or visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months9
    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: 84
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 36
    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 34
    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 Decision2017-09-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-12-01
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-09-04
    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-Sat Apr 20 13:26:04 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA