Hepatitis B Virus (HBV)Phase 3NCT00734162
Evaluation of Tenofovir Disoproxil Fumarate in Adolescents With Chronic Hepatitis B Infection
A Phase 3 study testing Tenofovir disoproxil fumarate (TDF) in people with Hepatitis B Virus (HBV), run by Gilead Sciences at 21 sites in 7 countries.
Trial summary
The primary purpose of the study is to evaluate the effectiveness, safety, and tolerability of tenofovir disoproxil fumarate (TDF) in adolescents (aged 12-17 years) with chronic hepatitis B virus (HBV) infection. The optimal treatment for adolescents with chronic HBV infection is currently unknown. Read more about this study
- Who is it for?
- Ages 12 to 17 years
- Conditions the study is for
- Hepatitis B Virus (HBV)
- What is being tested?
- Tenofovir disoproxil fumarate (TDF)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 21 sitesin 7 countries
- Study dates
- Dec 2008to Dec 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female, 12 through 17 years of age, inclusive (consent of parent/legal guardian required)
- Documented chronic HBV infection
- HBeAg positive or HBeAg negative
- Weight > 35 kg
- Able to swallow oral tablets
- HBV DNA > 100,000 copies/mL (polymerase chain reaction (PCR) method)
Show all 12Show fewer
- Alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN) at screening, OR any history of ALT > 2 × ULN over the past 24 months
- Willing and able to provide written informed consent/assent (child and parent/legal guardian)
- Negative serum pregnancy test (for postmenarchal females only)
- Estimated glomerular filtration rate (creatinine clearance [using the Schwartz formula]) > 80 mL/min/1.73m^2
- Adequate hematologic function (absolute neutrophil count ≥ 1,500/mm^3; hemoglobin ≥ 10.0 g/dL)
- No prior TDF therapy (participants may have received prior interferon or oral anti-HBV nucleoside/nucleotide therapy; participants must have discontinued interferon therapy ≥ 6 months prior to screening; participants experienced on anti-HBV nucleoside/nucleotide therapy must have discontinued therapy ≥ 16 weeks prior to screening to avoid flare if randomized to the placebo arm)
Who cannot join
- Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study
- Males and females of reproductive potential who are not willing to use an effective method of contraception during the study
- Decompensated liver disease
- Receipt of interferon (pegylated or not) therapy within 6 months of the Screening Visit
- Receipt of anti-HBV nucleoside/nucleotide therapy within 16 weeks of the Screening Visit
- Alpha fetoprotein > 50 ng/mL
Show all 16Show fewer
- Evidence of hepatocellular carcinoma (HCC)
- Coinfection with HIV, hepatitis C virus (HCV), or hepatitis D virus (HDV)
- History of significant renal disease (eg, nephrotic syndrome, renal dysgenesis, polycystic kidney disease, congenital nephrosis, acute tubular necrosis, other renal disease)
- History of significant bone disease (eg, osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochondroses, multiple bone fractures)
- Significant cardiovascular, pulmonary, or neurological disease
- Evidence of a gastrointestinal malabsorption syndrome that may interfere with absorption of orally administered medications
- History of solid organ or bone marrow transplantation
- Ongoing therapy with nephrotoxic agents, competitors of renal excretion, systemic chemotherapeutic agents, systemic corticosteroids, interleukin-2 (IL-2), or other immunomodulating or investigational agents
- Known hypersensitivity to the study drugs, the metabolites or formulation excipients
- Any other condition (including alcohol or substance abuse) or prior therapy that, in the opinion of the Investigator, would make the participants unsuitable for the study or unable to comply with dosing requirements
Trial locations and contacts
21 sites in 7 countries.
21 sites in 7 countries
Poland8 sites
Samodzielny Publiczny Dzieciecy Szpital Kliniczny Akademii Medycznej w Bialymstoku
Bialystok, 15-274
Wojewodzki Specjalistyczny Szpital im Bieganskiego
Bydgoszcz, 85-030
Wojewodzki Szpital Obserwacyjno-Zakazny im. T. Browicza
Bydgoszcz, 85-030
Krakowski Szpital Specjalistyczny im. Jana Pawla II
Krakow, 31-202
Samodzielny Publiczny Szpital Kliniczny im. Karola Johschera
Poznan, 60-572
Specjalistyczny Zespol Opieki Zdrowotnej nad Matka i Dzieckiem
Poznan, 61-734
Wojewodzki Szpital Zakazny
Warsaw, 01-201
Samodzielny Publiczny Szpital Kliniczny Nr 1
Wroclaw, 50-368
United States3 sites
Riley Hospital for Children
Indianapolis, Indiana, 46202
Children's Hospital & Research Center at Oakland
Oakland, California, 94609
Children's Hospital & Regional Medical Center, d/b/a Seattle Children's Research Institute
Seattle, Washington, 98105
Romania3 sites
Fundeni Clinical Institute
Bucharest, 022328
Institute for Infectious Diseases
Bucharest, 21105
Cluj Childrens Emergency Hospital
Napaco, 400217
Bulgaria2 sites
Multiprofile Hospital for Active Treatment Sveti Georgi
Plovdiv, 4002
Clinic of Gastroenterology, Specialized Hospital for Active Treatment of Pediatric Diseases, Sofia
Sofia, 1606
France2 sites
Hopital Femmes Meres Enfants
Bron, 69677
Hôpital Claude Huriez
Lille, 59037
Spain2 sites
Hosp Univ y Politecnico La Fe de Valencia
Madrid, 28046
Hospital Universitario De Getafe
Madrid, 46009
Turkey (Türkiye)1 site
Ege Universitesi Tip Fakultesi Hastanesi
Izmir, 35100
About this study
Official title: A Randomized, Double-Blind Evaluation of the Antiviral Efficacy, Safety, and Tolerability of Tenofovir Disoproxil Fumarate Versus Placebo in Adolescents With Chronic Hepatitis B Infection
The primary purpose of the study is to evaluate the effectiveness, safety, and tolerability of tenofovir disoproxil fumarate (TDF) in adolescents (aged 12-17 years) with chronic hepatitis B virus (HBV) infection.
The optimal treatment for adolescents with chronic HBV infection is currently unknown. Treatment with interferon alfa, lamivudine, and adefovir dipivoxil in pediatric populations has been shown to be less than optimal. Further, the safety and efficacy of entecavir and telbivudine have not been established in patients < 16 years of age. A study evaluating TDF in adolescents (ages 12-17) was needed to assess the safety and efficacy of this agent in the treatment of chronic hepatitis B in this patient population. In addition, the study will help to further elucidate the pharmacokinetic (PK) and resistance profiles of TDF. Through their participation, study participants will help generate critical new information to help guide the most optimal treatment of chronic HBV infection in adolescents.
This is a randomized, double-blind study to evaluate the antiviral efficacy, safety, and tolerability of TDF versus placebo in adolescents with chronic HBV infection. TDF treatment-naive participants were randomized in a 1:1 ratio to TDF or placebo. After 72 weeks of blinded treatment, participants were to switch to open-label TDF for an additional 2.5 years of treatment, provided that no safety concerns are identified by the Independent Data Monitoring Committee monitoring the study.
- Conditions
- Hepatitis B Virus (HBV)
- Being tested
- Tenofovir disoproxil fumarate (TDF), Placebo
- Keywords
- tenofovir, adolescents, chronic hepatitis B
- Medical subject headings
- Hepatitis B, Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir disoproxil fumarate (TDF)Drug
Also called Viread®
TDF administered as a 300-mg tablet once daily
PlaceboDrug
TDF placebo tablet once daily
| Study group | Role | What they receive |
|---|---|---|
| Tenofovir disoproxil fumarate (TDF) | Experimental | Not described Receives: Drug: Tenofovir disoproxil fumarate (TDF) |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 72
The percentage of participants with HBV DNA < 400 copies/mL at Week 72 was summarized by treatment and age group (grouped by baseline age for analysis), using the missing = failure (M = F) analysis with the double-blind efficacy evaluation (DBEE) algorithm.
In the M = F analysis method, all missing data were considered as failure to meet the outcome measure threshold. This method was combined with the DBEE algorithm, which included all available data for the double-blind period, and any data for the open-label period were not included; data generated during treatment-free follow-up from subjects who achieved HBsAg loss and entered treatment-free follow-up during double-blind treatment period were included.
Measured: Week 72
Percentage of Participants With at Least a 6% Decrease From Baseline in Bone Mineral Density (BMD) of the Spine at Week 72
Data were summarized by treatment and age group (grouped by baseline age for analysis).
In contrast with what was previously reported in the interim results posting, 1 participant met the primary safety endpoint of at least a 6% decrease from baseline in spine BMD at Week 72, based on the final BMD data analysis. The apparent discrepancy was due to the correction factor applied to the subject-specific BMD calculations performed at the time of the Interim Week 72 clinical study report that could not take into account the actual Week 72 phantom data (ie, calibration test used in longitudinal clinical trials to monitor and adjust for shifts in the dual-energy x-ray absorptiometry (DXA) scanner calibration over time), which were not provided by the site at that time. The correction factor applied to the final analysis has been properly based on all phantom data through the end of Week 72, as well as through the end of Week 192.
Measured: Baseline to Week 72
Secondary outcomes (35)
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, 144, and 192
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
Measured: Weeks 48, 96, 144, and 192
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 72, 96, 144, and 192
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
Measured: Weeks 48, 72, 96, 144, and 192
Percentage of Participants With HBV DNA < 400 Copies/mL and Normal ALT at Weeks 48, 72, 96, 144, and 192
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
Measured: Weeks 48, 72, 96, 144, and 192
Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 72, 96, 144, and 192
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
Measured: Weeks 48, 72, 96, 144, and 192
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 72, 96, 144, and 192
Data were summarized by treatment and age group (grouped by baseline age for analysis), using the M = F.
Measured: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants With HBsAg Seroconversion at Weeks 48, 72, 96, 144, and 192
HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive. Data were summarized by treatment and age group (grouped by baseline age for analysis), using the M = F.
Measured: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants With at Least a 6% Decrease From Baseline in Spine BMD at Weeks 48, 96, 144, and 192
The percentage of participants reported is the cumulative incidence from baseline to the respective time point. Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Weeks 48, 96, 144, and 192
Percentage of Participants With at Least a 6% Decrease From Baseline in Whole Body BMD at Weeks 48, 72, 96, 144, and 192
The percentage of participants reported is the cumulative incidence from baseline to the respective time point. Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Weeks 48, 72, 96, 144, and 192
Percent Change From Baseline in Spine Bone Mineral Density (BMD) at Week 48
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 48
Percent Change From Baseline in Spine BMD at Week 72
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 72
Percent Change From Baseline in Spine BMD at Week 96
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 96
Percent Change From Baseline in Spine BMD at Week 144
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 144
Percent Change From Baseline in Spine BMD at Week 192
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 192
Percent Change From Baseline in Whole Body BMD at Week 48
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 48
Percent Change From Baseline in Whole Body BMD at Week 72
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 72
Percent Change From Baseline in Whole Body BMD at Week 96
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 96
Percent Change From Baseline in Whole Body BMD at Week 144
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 144
Percent Change From Baseline in Whole Body BMD at Week 192
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 192
Change From Baseline in Z-score for Spine BMD at Week 48
To assess any effect of treatment on growth, Z-scores were used to express the deviation from a reference population for lumbar spine BMD. A Z-score of 0 indicated that a subject was typical of the population for their age, ethnicity, and gender. A negative Z-score indicated that the subject's recorded value was lower than typical for their age, ethnicity, and gender. A positive Z-score indicates that the subject's recorded value was higher than typical for their age, ethnicity, and gender. Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 48
Change From Baseline in Z-score for Spine BMD at Week 72
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 72
Change From Baseline in Z-score for Spine BMD at Week 96
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 96
Change From Baseline in Z-score for Spine BMD at Week 144
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 144
Change From Baseline in Z-score for Spine BMD at Week 192
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 192
Change From Baseline in Z-score for Whole Body BMD at Week 48
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 48
Change From Baseline in Z-score for Whole Body BMD at Week 72
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 72
Change From Baseline in Z-score for Whole Body BMD at Week 96
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 96
Change From Baseline in Z-score for Whole Body BMD at Week 144
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 144
Change From Baseline in Z-score for Whole Body BMD at Week 192
Data were summarized by treatment and age group (grouped by baseline age for analysis).
Measured: Baseline; Week 192
Number of Participants With Changes in Drug-Resistant Mutations During the Study
The number of participants with changes in drug-resistant mutations during the study was summarized.
Measured: Baseline through Week 192
Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Loss at Weeks 48, 72, 96, 144, and 192
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
Measured: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Seroconversion at Weeks 48, 72, 96, 144, and 192
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
Measured: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants Who Were HBeAg-Positive at Baseline Who Had HBV DNA < 400 Copies/mL, Normal ALT, and HBeAg Loss/Seroconversion at Weeks 48, 72, 96, 144, and 192
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
Measured: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants With Abnormal ALT at Baseline Who Had Normalized ALT at Weeks 48, 72, 96, 144, and 192
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
Measured: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants With Abnormal ALT at Baseline Who Had HBV DNA < 400 Copies/mL and Normalized ALT at Weeks 48, 72, 96, 144, and 192
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
Measured: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants Who Were HBeAg-Positive With Abnormal ALT at Baseline Who Had HBV DNA < 400 Copies/mL, Normalized ALT, and HBeAg Loss/Seroconversion at Weeks 48, 72, 96, 144, and 192
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
Measured: Baseline; Weeks 48, 72, 96, 144, and 192
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2008 (estimated)
- Study startDec 2008
- Primary completionMar 2011
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis B Virus (HBV)Studies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Benedetta Massetto, MD, PhD, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00734162
- Sponsor's protocol ID
- GS-US-174-0115
- Status last verified
- Jul 2016
- First submitted
- 13 Aug 2008
- Last updated
- 1 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Murray KF, Szenborn L, Wysocki J, Rossi S, Corsa AC, Dinh P, McHutchison J, Pang PS, Luminos LM, Pawlowska M, Mizerski J. Randomized, placebo-controlled trial of tenofovir disoproxil fumarate in adolescents with chronic hepatitis B. Hepatology. 2012 Dec;56(6):2018-26. doi: 10.1002/hep.25818. Epub 2012 Aug 27.
PubMed 22544804
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind Evaluation of the Antiviral Efficacy, Safety, and Tolerability of Tenofovir Disoproxil Fumarate Versus Placebo in Adolescents With Chronic Hepatitis B Infection
- ClinicalTrials.gov ID
- NCT00734162
- Acronym / sponsor ID
- GS-US-174-0115
- Conditions
- Hepatitis B Virus (HBV)
- Keywords
- tenofovir, adolescents, chronic hepatitis B
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- Mar 2011 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 14 Aug 2008 (estimated)
- Results
- Posted 7 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of the study is to evaluate the effectiveness, safety, and tolerability of tenofovir disoproxil fumarate (TDF) in adolescents (aged 12-17 years) with chronic hepatitis B virus (HBV) infection.
The optimal treatment for adolescents with chronic HBV infection is currently unknown. Treatment with interferon alfa, lamivudine, and adefovir dipivoxil in pediatric populations has been shown to be less than optimal. Further, the safety and efficacy of entecavir and telbivudine have not been established in patients < 16 years of age. A study evaluating TDF in adolescents (ages 12-17) was needed to assess the safety and efficacy of this agent in the treatment of chronic hepatitis B in this patient population. In addition, the study will help to further elucidate the pharmacokinetic (PK) and resistance profiles of TDF. Through their participation, study participants will help generate critical new information to help guide the most optimal treatment of chronic HBV infection in adolescents.
This is a randomized, double-blind study to evaluate the antiviral efficacy, safety, and tolerability of TDF versus placebo in adolescents with chronic HBV infection. TDF treatment-naive participants were randomized in a 1:1 ratio to TDF or placebo. After 72 weeks of blinded treatment, participants were to switch to open-label TDF for an additional 2.5 years of treatment, provided that no safety concerns are identified by the Independent Data Monitoring Committee monitoring the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tenofovir disoproxil fumarate (TDF) | Experimental | Drug: Tenofovir disoproxil fumarate (TDF) |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 12 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- Male or female, 12 through 17 years of age, inclusive (consent of parent/legal guardian required)
- Documented chronic HBV infection
- HBeAg positive or HBeAg negative
- Weight > 35 kg
- Able to swallow oral tablets
Key exclusion criteria (16 listed)
- Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study
- Males and females of reproductive potential who are not willing to use an effective method of contraception during the study
- Decompensated liver disease
- Receipt of interferon (pegylated or not) therapy within 6 months of the Screening Visit
- Receipt of anti-HBV nucleoside/nucleotide therapy within 16 weeks of the Screening Visit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir disoproxil fumarate (TDF)Also: Viread®TDF administered as a 300-mg tablet once daily | Drug | Tenofovir disoproxil fumarate (TDF) |
| PlaceboTDF placebo tablet once daily | Drug | Placebo |
Primary outcome
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 72
Time frame: Week 72
The percentage of participants with HBV DNA < 400 copies/mL at Week 72 was summarized by treatment and age group (grouped by baseline age for analysis), using the missing = failure (M = F) analysis with the double-blind efficacy evaluation (DBEE) algorithm. In the M = F analysis method, all missing data were considered as failure to meet the outcome measure threshold. This method was combined with the DBEE algorithm, which included all available data for the double-blind period, and any data for the open-label period were not included; data generated during treatment-free follow-up from subjects who achieved HBsAg loss and entered treatment-free follow-up during double-blind treatment period were included.
Percentage of Participants With at Least a 6% Decrease From Baseline in Bone Mineral Density (BMD) of the Spine at Week 72
Time frame: Baseline to Week 72
Data were summarized by treatment and age group (grouped by baseline age for analysis). In contrast with what was previously reported in the interim results posting, 1 participant met the primary safety endpoint of at least a 6% decrease from baseline in spine BMD at Week 72, based on the final BMD data analysis. The apparent discrepancy was due to the correction factor applied to the subject-specific BMD calculations performed at the time of the Interim Week 72 clinical study report that could not take into account the actual Week 72 phantom data (ie, calibration test used in longitudinal clinical trials to monitor and adjust for shifts in the dual-energy x-ray absorptiometry (DXA) scanner calibration over time), which were not provided by the site at that time. The correction factor applied to the final analysis has been properly based on all phantom data through the end of Week 72, as well as through the end of Week 192.
35 secondary outcomes
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, 144, and 192
Time frame: Weeks 48, 96, 144, and 192
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 72, 96, 144, and 192
Time frame: Weeks 48, 72, 96, 144, and 192
Percentage of Participants With HBV DNA < 400 Copies/mL and Normal ALT at Weeks 48, 72, 96, 144, and 192
Time frame: Weeks 48, 72, 96, 144, and 192
Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 72, 96, 144, and 192
Time frame: Weeks 48, 72, 96, 144, and 192
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 72, 96, 144, and 192
Time frame: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants With HBsAg Seroconversion at Weeks 48, 72, 96, 144, and 192
Time frame: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants With at Least a 6% Decrease From Baseline in Spine BMD at Weeks 48, 96, 144, and 192
Time frame: Baseline; Weeks 48, 96, 144, and 192
Percentage of Participants With at Least a 6% Decrease From Baseline in Whole Body BMD at Weeks 48, 72, 96, 144, and 192
Time frame: Baseline; Weeks 48, 72, 96, 144, and 192
Percent Change From Baseline in Spine Bone Mineral Density (BMD) at Week 48
Time frame: Baseline; Week 48
Percent Change From Baseline in Spine BMD at Week 72
Time frame: Baseline; Week 72
Percent Change From Baseline in Spine BMD at Week 96
Time frame: Baseline; Week 96
Percent Change From Baseline in Spine BMD at Week 144
Time frame: Baseline; Week 144
Percent Change From Baseline in Spine BMD at Week 192
Time frame: Baseline; Week 192
Percent Change From Baseline in Whole Body BMD at Week 48
Time frame: Baseline; Week 48
Percent Change From Baseline in Whole Body BMD at Week 72
Time frame: Baseline; Week 72
Percent Change From Baseline in Whole Body BMD at Week 96
Time frame: Baseline; Week 96
Percent Change From Baseline in Whole Body BMD at Week 144
Time frame: Baseline; Week 144
Percent Change From Baseline in Whole Body BMD at Week 192
Time frame: Baseline; Week 192
Change From Baseline in Z-score for Spine BMD at Week 48
Time frame: Baseline; Week 48
Change From Baseline in Z-score for Spine BMD at Week 72
Time frame: Baseline; Week 72
Change From Baseline in Z-score for Spine BMD at Week 96
Time frame: Baseline; Week 96
Change From Baseline in Z-score for Spine BMD at Week 144
Time frame: Baseline; Week 144
Change From Baseline in Z-score for Spine BMD at Week 192
Time frame: Baseline; Week 192
Change From Baseline in Z-score for Whole Body BMD at Week 48
Time frame: Baseline; Week 48
Change From Baseline in Z-score for Whole Body BMD at Week 72
Time frame: Baseline; Week 72
Change From Baseline in Z-score for Whole Body BMD at Week 96
Time frame: Baseline; Week 96
Change From Baseline in Z-score for Whole Body BMD at Week 144
Time frame: Baseline; Week 144
Change From Baseline in Z-score for Whole Body BMD at Week 192
Time frame: Baseline; Week 192
Number of Participants With Changes in Drug-Resistant Mutations During the Study
Time frame: Baseline through Week 192
Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Loss at Weeks 48, 72, 96, 144, and 192
Time frame: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Seroconversion at Weeks 48, 72, 96, 144, and 192
Time frame: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants Who Were HBeAg-Positive at Baseline Who Had HBV DNA < 400 Copies/mL, Normal ALT, and HBeAg Loss/Seroconversion at Weeks 48, 72, 96, 144, and 192
Time frame: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants With Abnormal ALT at Baseline Who Had Normalized ALT at Weeks 48, 72, 96, 144, and 192
Time frame: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants With Abnormal ALT at Baseline Who Had HBV DNA < 400 Copies/mL and Normalized ALT at Weeks 48, 72, 96, 144, and 192
Time frame: Baseline; Weeks 48, 72, 96, 144, and 192
Percentage of Participants Who Were HBeAg-Positive With Abnormal ALT at Baseline Who Had HBV DNA < 400 Copies/mL, Normalized ALT, and HBeAg Loss/Seroconversion at Weeks 48, 72, 96, 144, and 192
Time frame: Baseline; Weeks 48, 72, 96, 144, and 192
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22544804Murray KF, Szenborn L, Wysocki J, Rossi S, Corsa AC, Dinh P, McHutchison J, Pang PS, Luminos LM, Pawlowska M, Mizerski J. Randomized, placebo-controlled trial of tenofovir disoproxil fumarate in adolescents with chronic hepatitis B. Hepatology. 2012 Dec;56(6):2018-26. doi: 10.1002/hep.25818. Epub 2012 Aug 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benedetta Massetto, MD, PhD study director
Gilead Sciences
21 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tenofovir disoproxil fumarate (TDF) in people with Hepatitis B Virus (HBV), run by Gilead Sciences at 21 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Poland, United States, Romania, Bulgaria, France and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 72 (time frame: Week 72). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00734162, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2016.