Evaluation of Tenofovir Disoproxil Fumarate in Adolescents With Chronic Hepatitis B Infection
- Conditions
- Hepatitis B Virus (HBV)
- Interventions
- Drug: Placebo
- Registration Number
- NCT00734162
- Lead Sponsor
- Gilead Sciences
- Brief 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. 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 106
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tenofovir disoproxil fumarate (TDF) Tenofovir disoproxil fumarate (TDF) - Placebo Placebo -
- Primary Outcome Measures
Name Time Method Percentage of Participants With HBV DNA < 400 Copies/mL at Week 72 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 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, 144, and 192 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.
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 72, 96, 144, and 192 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.
Percentage of Participants With HBV DNA < 400 Copies/mL and Normal ALT at Weeks 48, 72, 96, 144, and 192 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.
Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 72, 96, 144, and 192 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.
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 72, 96, 144, and 192 Baseline; 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.
Percentage of Participants With HBsAg Seroconversion at Weeks 48, 72, 96, 144, and 192 Baseline; 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.
Percentage of Participants With at Least a 6% Decrease From Baseline in Spine BMD at Weeks 48, 96, 144, and 192 Baseline; 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).
Percentage of Participants With at Least a 6% Decrease From Baseline in Whole Body BMD at Weeks 48, 72, 96, 144, and 192 Baseline; 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).
Percent Change From Baseline in Spine Bone Mineral Density (BMD) at Week 48 Baseline; Week 48 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Percent Change From Baseline in Spine BMD at Week 72 Baseline; Week 72 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Percent Change From Baseline in Spine BMD at Week 96 Baseline; Week 96 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Percent Change From Baseline in Spine BMD at Week 144 Baseline; Week 144 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Percent Change From Baseline in Spine BMD at Week 192 Baseline; Week 192 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Percent Change From Baseline in Whole Body BMD at Week 48 Baseline; Week 48 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Percent Change From Baseline in Whole Body BMD at Week 72 Baseline; Week 72 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Percent Change From Baseline in Whole Body BMD at Week 96 Baseline; Week 96 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Percent Change From Baseline in Whole Body BMD at Week 144 Baseline; Week 144 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Percent Change From Baseline in Whole Body BMD at Week 192 Baseline; Week 192 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Change From Baseline in Z-score for Spine BMD at Week 48 Baseline; 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).
Change From Baseline in Z-score for Spine BMD at Week 72 Baseline; Week 72 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Change From Baseline in Z-score for Spine BMD at Week 96 Baseline; Week 96 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Change From Baseline in Z-score for Spine BMD at Week 144 Baseline; Week 144 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Change From Baseline in Z-score for Spine BMD at Week 192 Baseline; Week 192 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Change From Baseline in Z-score for Whole Body BMD at Week 48 Baseline; Week 48 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Change From Baseline in Z-score for Whole Body BMD at Week 72 Baseline; Week 72 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Change From Baseline in Z-score for Whole Body BMD at Week 96 Baseline; Week 96 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Change From Baseline in Z-score for Whole Body BMD at Week 144 Baseline; Week 144 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Change From Baseline in Z-score for Whole Body BMD at Week 192 Baseline; Week 192 Data were summarized by treatment and age group (grouped by baseline age for analysis).
Number of Participants With Changes in Drug-Resistant Mutations During the Study Baseline through Week 192 The number of participants with changes in drug-resistant mutations during the study was summarized.
Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Loss at Weeks 48, 72, 96, 144, and 192 Baseline; 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.
Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Seroconversion at Weeks 48, 72, 96, 144, and 192 Baseline; 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.
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 Baseline; 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.
Percentage of Participants With Abnormal ALT at Baseline Who Had Normalized ALT at Weeks 48, 72, 96, 144, and 192 Baseline; 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.
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 Baseline; 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.
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 Baseline; 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.
Trial Locations
- Locations (21)
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Hopital Femmes Meres Enfants
🇫🇷Bron Cedex, France
Hospital Universitario De Getafe
🇪🇸Madrid, Spain
Multiprofile Hospital for Active Treatment Sveti Georgi
🇧🇬Plovdiv, Bulgaria
Specjalistyczny Zespol Opieki Zdrowotnej nad Matka i Dzieckiem
🇵🇱Poznań, Poland
Hosp Univ y Politecnico La Fe de Valencia
🇪🇸Madrid, Spain
Children's Hospital & Regional Medical Center, d/b/a Seattle Children's Research Institute
🇺🇸Seattle, Washington, United States
Hôpital Claude Huriez
🇫🇷Lille Cedex, France
Samodzielny Publiczny Dzieciecy Szpital Kliniczny Akademii Medycznej w Bialymstoku
🇵🇱Białystok, Poland
Krakowski Szpital Specjalistyczny im. Jana Pawla II
🇵🇱Kraków, Poland
Wojewodzki Szpital Obserwacyjno-Zakazny im. T. Browicza
🇵🇱Bydgoszcz, Poland
Wojewodzki Szpital Zakazny
🇵🇱Warszawa, Poland
Ege Universitesi Tip Fakultesi Hastanesi
🇹🇷Izmir, Turkey
Children's Hospital & Research Center at Oakland
🇺🇸Oakland, California, United States
Fundeni Clinical Institute
🇷🇴Bucharest, Romania
Clinic of Gastroenterology, Specialized Hospital for Active Treatment of Pediatric Diseases, Sofia
🇧🇬Sofia, Bulgaria
Samodzielny Publiczny Szpital Kliniczny im. Karola Johschera
🇵🇱Poznan, Poland
Institute for Infectious Diseases
🇷🇴Bucharest, Romania
Samodzielny Publiczny Szpital Kliniczny Nr 1
🇵🇱Wrocław, Poland
Cluj Childrens Emergency Hospital
🇷🇴Napaco, Romania
Wojewodzki Specjalistyczny Szpital im Bieganskiego
🇵🇱Bydgoszcz, Poland