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   44334   clinical trials with a EudraCT protocol, of which   7366   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

    Download PDF

    Clinical Trial Results:
    Pharmacoepidemiology study to define the long-term safety profile of tenofovir disoproxil fumarate (Tenofovir DF, Viread®) and describe the management of Tenofovir DF-associated renal and bone toxicity in Chronic Hepatitis B (CHB)-infected adolescents aged 12 to <18 years in Europe

    Summary
    EudraCT number
    2014-004939-39
    Trial protocol
    BE   GB   ES   BG   GR   FR   IT  
    Global end of trial date
    11 Apr 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    24 Oct 2018
    First version publication date
    24 Oct 2018
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    GS-EU-174-1403
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02479880
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Gilead Sciences
    Sponsor organisation address
    333 Lakeside Drive, Foster City, CA, United States, 94404
    Public contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Scientific contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    11 Apr 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Feb 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Apr 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this trial was to characterize the long term (i.e., 96 weeks of follow up) bone safety profile of open-label tenofovir disoproxil fumarate (DF) treatment of adolescents with chronic hepatitis B (CHB) infection. This includes prospectively evaluating and comparing the bone mineral density (BMD) change between adolescents with CHB 12 to < 18 years of age treated with tenofovir DF in European treatment centers who are assigned to one of two schedules for renal and bone laboratory monitoring and BMD measurement. Primary study outcome will be the percent changes in BMD from Baseline through study Week 96.
    Protection of trial subjects
    The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements. This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    03 Jul 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Romania: 8
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    Greece: 2
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    France: 3
    Worldwide total number of subjects
    30
    EEA total number of subjects
    30
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    30
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Participants were enrolled at study sites in Europe. The first participant was screened on 03 July 2015. The last study visit occurred on 11 April 2018. The study did not achieve targeted enrollment as it was prematurely terminated by the Pharmacovigilance Risk Assessment Committee (PRAC).

    Pre-assignment
    Screening details
    35 participants were screened.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Tenofovir DF + Increased Bone/Renal Monitoring
    Arm description
    One 300 mg tablet given once daily for up to 96 weeks + laboratory bone biomarker testing and lumbar spine and whole-body dual-energy x-ray absorptiometry (DXA) scans every 24 weeks from baseline to Week 96 (5 scans), and monitoring of renal function at 4 and 12 weeks after baseline and every 12 weeks thereafter. With the exception of an enhanced monitoring protocol for bone and renal outcomes, participants will be managed according to local standards of care.
    Arm type
    Experimental

    Investigational medicinal product name
    Tenofovir disoproxil fumarate
    Investigational medicinal product code
    Other name
    Viread®, TDF
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg once daily

    Arm title
    Tenofovir DF + Prespecified Bone Monitoring
    Arm description
    One 300 mg tablet given once daily for up to 96 weeks + laboratory bone biomarker testing and lumbar spine and whole-body DXA scans at baseline, Week 48, and Week 96. With the exception of pre-specified bone monitoring, participants will be managed according to local standards of care.
    Arm type
    Experimental

    Investigational medicinal product name
    Tenofovir disoproxil fumarate
    Investigational medicinal product code
    Other name
    Viread®, TDF
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg once daily

    Number of subjects in period 1
    Tenofovir DF + Increased Bone/Renal Monitoring Tenofovir DF + Prespecified Bone Monitoring
    Started
    15
    15
    Completed
    2
    2
    Not completed
    13
    13
         Pregnancy
    -
    1
         Study Terminated by Sponsor
    13
    12

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Tenofovir DF + Increased Bone/Renal Monitoring
    Reporting group description
    One 300 mg tablet given once daily for up to 96 weeks + laboratory bone biomarker testing and lumbar spine and whole-body dual-energy x-ray absorptiometry (DXA) scans every 24 weeks from baseline to Week 96 (5 scans), and monitoring of renal function at 4 and 12 weeks after baseline and every 12 weeks thereafter. With the exception of an enhanced monitoring protocol for bone and renal outcomes, participants will be managed according to local standards of care.

    Reporting group title
    Tenofovir DF + Prespecified Bone Monitoring
    Reporting group description
    One 300 mg tablet given once daily for up to 96 weeks + laboratory bone biomarker testing and lumbar spine and whole-body DXA scans at baseline, Week 48, and Week 96. With the exception of pre-specified bone monitoring, participants will be managed according to local standards of care.

    Reporting group values
    Tenofovir DF + Increased Bone/Renal Monitoring Tenofovir DF + Prespecified Bone Monitoring Total
    Number of subjects
    15 15 30
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    14 ( 1.4 ) 14 ( 1.5 ) -
    Gender categorical
    Units: Subjects
        Female
    5 5 10
        Male
    10 10 20

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Tenofovir DF + Increased Bone/Renal Monitoring
    Reporting group description
    One 300 mg tablet given once daily for up to 96 weeks + laboratory bone biomarker testing and lumbar spine and whole-body dual-energy x-ray absorptiometry (DXA) scans every 24 weeks from baseline to Week 96 (5 scans), and monitoring of renal function at 4 and 12 weeks after baseline and every 12 weeks thereafter. With the exception of an enhanced monitoring protocol for bone and renal outcomes, participants will be managed according to local standards of care.

    Reporting group title
    Tenofovir DF + Prespecified Bone Monitoring
    Reporting group description
    One 300 mg tablet given once daily for up to 96 weeks + laboratory bone biomarker testing and lumbar spine and whole-body DXA scans at baseline, Week 48, and Week 96. With the exception of pre-specified bone monitoring, participants will be managed according to local standards of care.

    Primary: Percentage of Participants with Bone-Related Adverse Events and/or a ≥ 4% Reduction in BMD from Baseline to Week 96

    Close Top of page
    End point title
    Percentage of Participants with Bone-Related Adverse Events and/or a ≥ 4% Reduction in BMD from Baseline to Week 96 [1]
    End point description
    Participants in the Safety Analysis Set (participants who were randomized into the study and received at least one dose of Viread) with available data were analyzed.
    End point type
    Primary
    End point timeframe
    Week 96
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Because this study did not achieve targeted enrollment as it was prematurely terminated by the PRAC, the statistical analysis for this endpoint was not performed.
    End point values
    Tenofovir DF + Increased Bone/Renal Monitoring Tenofovir DF + Prespecified Bone Monitoring
    Number of subjects analysed
    15
    15
    Units: percentage of participants
        number (not applicable)
    6.7
    0
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    96 weeks + 30 days
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Tenofovir DF + Increased Bone/Renal Monitoring
    Reporting group description
    One 300 mg tablet given once daily for up to 96 weeks + laboratory bone biomarker testing and lumbar spine and whole-body DXA scans every 24 weeks from baseline to Week 96 (5 scans), and monitoring of renal function at 4 and 12 weeks after baseline and every 12 weeks thereafter. With the exception of an enhanced monitoring protocol for bone and renal outcomes, participants will be managed according to local standards of care.

    Reporting group title
    Tenofovir DF + Prespecified Bone Monitoring
    Reporting group description
    One 300 mg tablet given once daily for up to 96 weeks + laboratory bone biomarker testing and lumbar spine and whole-body DXA scans at baseline, Week 48, and Week 96. With the exception of pre-specified bone monitoring, participants will be managed according to local standards of care.

    Serious adverse events
    Tenofovir DF + Increased Bone/Renal Monitoring Tenofovir DF + Prespecified Bone Monitoring
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 15 (6.67%)
    2 / 15 (13.33%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Calcinosis
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Tenofovir DF + Increased Bone/Renal Monitoring Tenofovir DF + Prespecified Bone Monitoring
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 15 (66.67%)
    10 / 15 (66.67%)
    Investigations
    Vitamin D decreased
         subjects affected / exposed
    2 / 15 (13.33%)
    2 / 15 (13.33%)
         occurrences all number
    4
    3
    Bone density decreased
         subjects affected / exposed
    0 / 15 (0.00%)
    2 / 15 (13.33%)
         occurrences all number
    0
    2
    Injury, poisoning and procedural complications
    Forearm fracture
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 15 (0.00%)
    2 / 15 (13.33%)
         occurrences all number
    0
    2
    Somnolence
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Syncope
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    Tremor
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    Fatigue
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 15 (6.67%)
    2 / 15 (13.33%)
         occurrences all number
    2
    2
    Vomiting
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    Abdominal pain lower
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Anal fissure
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    Diarrhoea
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Dyschezia
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Food poisoning
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Dyspareunia
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Muscle contracture
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    Pharyngitis
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 15 (6.67%)
         occurrences all number
    1
    1
    Ear infection
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    Otitis media
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Viral infection
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Vitamin D deficiency
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Feb 2015
    Serum renal chemistry (i.e., glucose, creatinine, calculated creatinine clearance): at 4 weeks and 12 weeks from Baseline and every 12 weeks thereafter [changed from every 4 weeks from Baseline to Week 48 and every 12 weeks thereafter]. Urinalysis (i.e., protein, glucose, creatinine, phosphate, bicarbonate, blood): at 4 weeks and 12 weeks from Baseline and every 12 weeks thereafter [changed from every 4 weeks from Baseline to Week 48 and every 12 weeks thereafter]. Clarification of pregnancy screening (after Baseline) as a urine screen wherever referenced. Clarification to recommend a fasted state for collecting serum renal chemistry and urinalysis, serum bone chemistry. Clarification that DXA should be performed +/- 14 days from the scheduled clinic visit.
    10 Mar 2015
    Revised reference to the study drug through out the protocol. Changed from 245 mg tenofovir disoproxil to 300 mg tenofovir disoproxil fumarate, tenofovir DF (Viread®), which is equivalent to 245 mg tenofovir disoproxil.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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-Sun May 04 22:50:25 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA