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
Overview
- Phase
- Phase 3
- Intervention
- Tenofovir disoproxil fumarate (TDF)
- Conditions
- Hepatitis B Virus (HBV)
- Sponsor
- Gilead Sciences
- Enrollment
- 106
- Locations
- 21
- Primary Endpoint
- Percentage of Participants With HBV DNA < 400 Copies/mL at Week 72
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Tenofovir disoproxil fumarate (TDF)
Intervention: Tenofovir disoproxil fumarate (TDF)
Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, 144, and 192(Weeks 48, 96, 144, and 192)
- Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 72, 96, 144, and 192(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(Weeks 48, 72, 96, 144, and 192)
- Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 72, 96, 144, and 192(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(Baseline; Weeks 48, 72, 96, 144, and 192)
- Percentage of Participants With HBsAg Seroconversion at Weeks 48, 72, 96, 144, and 192(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(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(Baseline; Weeks 48, 72, 96, 144, and 192)
- Percent Change From Baseline in Spine Bone Mineral Density (BMD) at Week 48(Baseline; Week 48)
- Percent Change From Baseline in Spine BMD at Week 72(Baseline; Week 72)
- Percent Change From Baseline in Spine BMD at Week 96(Baseline; Week 96)
- Percent Change From Baseline in Spine BMD at Week 144(Baseline; Week 144)
- Percent Change From Baseline in Spine BMD at Week 192(Baseline; Week 192)
- Percent Change From Baseline in Whole Body BMD at Week 48(Baseline; Week 48)
- Percent Change From Baseline in Whole Body BMD at Week 72(Baseline; Week 72)
- Percent Change From Baseline in Whole Body BMD at Week 96(Baseline; Week 96)
- Percent Change From Baseline in Whole Body BMD at Week 144(Baseline; Week 144)
- Percent Change From Baseline in Whole Body BMD at Week 192(Baseline; Week 192)
- Change From Baseline in Z-score for Spine BMD at Week 48(Baseline; Week 48)
- Change From Baseline in Z-score for Spine BMD at Week 72(Baseline; Week 72)
- Change From Baseline in Z-score for Spine BMD at Week 96(Baseline; Week 96)
- Change From Baseline in Z-score for Spine BMD at Week 144(Baseline; Week 144)
- Change From Baseline in Z-score for Spine BMD at Week 192(Baseline; Week 192)
- Change From Baseline in Z-score for Whole Body BMD at Week 48(Baseline; Week 48)
- Change From Baseline in Z-score for Whole Body BMD at Week 72(Baseline; Week 72)
- Change From Baseline in Z-score for Whole Body BMD at Week 96(Baseline; Week 96)
- Change From Baseline in Z-score for Whole Body BMD at Week 144(Baseline; Week 144)
- Change From Baseline in Z-score for Whole Body BMD at Week 192(Baseline; Week 192)
- Number of Participants With Changes in Drug-Resistant Mutations During the Study(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(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(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(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(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(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(Baseline; Weeks 48, 72, 96, 144, and 192)