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
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EudraCT number |
2014-004939-39 |
Trial protocol |
BE GB ES BG GR FR IT |
Global end of trial date |
11 Apr 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Oct 2018
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First version publication date |
24 Oct 2018
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GS-EU-174-1403
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02479880 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Gilead Sciences
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Sponsor organisation address |
333 Lakeside Drive, Foster City, CA, United States, 94404
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Public contact |
Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
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Scientific contact |
Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
11 Apr 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
28 Feb 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Apr 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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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.
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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.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Jul 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Romania: 8
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Country: Number of subjects enrolled |
Spain: 6
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Country: Number of subjects enrolled |
United Kingdom: 6
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Country: Number of subjects enrolled |
Belgium: 4
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Country: Number of subjects enrolled |
Greece: 2
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Country: Number of subjects enrolled |
Italy: 1
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Country: Number of subjects enrolled |
France: 3
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Worldwide total number of subjects |
30
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EEA total number of subjects |
30
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
30
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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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
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Screening details |
35 participants were screened. | ||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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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
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Investigational medicinal product code |
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Other name |
Viread®, TDF
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
300 mg once daily
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Arm title
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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
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Investigational medicinal product code |
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Other name |
Viread®, TDF
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
300 mg once daily
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Baseline characteristics reporting groups
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Reporting group title |
Tenofovir DF + Increased Bone/Renal Monitoring
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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
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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. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tenofovir DF + Increased Bone/Renal Monitoring
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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
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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. |
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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.
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End point type |
Primary
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End point timeframe |
Week 96
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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. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
96 weeks + 30 days
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
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Reporting groups
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Reporting group title |
Tenofovir DF + Increased Bone/Renal Monitoring
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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
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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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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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.
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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. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |