Overview

This trial is active, not recruiting.

Condition hepatitis b virus (hbv)
Treatments tenofovir disoproxil fumarate (tdf), placebo
Phase phase 3
Sponsor Gilead Sciences
Start date September 2008
End date March 2011
Trial size 106 participants
Trial identifier NCT00734162, GS-US-174-0115

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. One hundred TDF treatment-naive participants were randomized in a 1:1 ratio to TDF or placebo. After 72 weeks of blinded treatment, all 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
tenofovir disoproxil fumarate (tdf) Viread
TDF administered as a 300-mg tablet, once daily (QD)
(Placebo Comparator)
placebo
Placebo to match TDF QD

Primary Outcomes

Measure
Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) < 400 Copies/mL at Week 72
time frame: Week 72
Number 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

Secondary Outcomes

Measure
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48
time frame: Week 48
Percentage of Participants With HBV DNA < 169 Copies/mL at Week 48
time frame: Week 48
Percentage of Participants With HBV DNA < 169 Copies/mL at Week 72
time frame: Week 72
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48
time frame: Week 48
Percentage of Participants With Normal ALT at Week 72
time frame: Week 72
Percentage of Participants With Abnormal ALT at Baseline Who Had Normalized ALT at Week 48
time frame: Baseline to Week 48
Percentage of Participants With Abnormal ALT at Baseline Who Had Normalized ALT at Week 72
time frame: Baseline to Week 72
Percentage of Participants With HBV DNA < 400 Copies/mL and Normal ALT at Week 48
time frame: Week 48
Percentage of Participants With HBV DNA < 400 Copies/mL and Normal ALT at Week 72
time frame: Week 72
Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Week 48
time frame: Baseline to Week 48
Percentage of Participants With HBsAg Loss at Week 72
time frame: Baseline to Week 72
Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Week 48
time frame: Baseline to Week 48
Percentage of Participants With Seroconversion to Anti-HBs at Week 72
time frame: Baseline to Week 72
Percentage of Participants Who Were HBV Early Antigen (HBeAg) Positive at Baseline and Who Had HBeAg Loss at Week 48
time frame: Baseline to Week 48
Percentage of Participants Who Were HBeAg Positive at Baseline and Who Had HBeAg Loss at Week 72
time frame: Baseline to Week 72
Percentage of Participants Who Were HBeAg Positive at Baseline and Who Had Seroconversion to Antibody Against HBV Early Antigen (Anti-HBe) at Week 48
time frame: Baseline to Week 48
Percentage of Participants Who Were HBeAg Positive at Baseline and Who Had Seroconversion to Anti-HBe at Week 72
time frame: Baseline to Week 72
Percentage of Participants Who Were HBeAg Positive at Baseline and Who Had HBV DNA < 400 Copies/mL, Normal ALT, and HBeAg Loss at Week 48
time frame: Baseline to Week 48
Percentage of Participants Who Were HBeAg Positive at Baseline and Who Had HBV DNA < 400 Copies/mL, Normal ALT, and HBeAg Loss at Week 72
time frame: Baseline to Week 72
Percentage of Participants Who Were HBeAg Positive at Baseline and Who Had HBV DNA < 400 Copies/mL, Normal ALT, and Seroconversion to HBeAg at Week 48
time frame: Baseline to Week 48
Percentage of Participants Who Were HBeAg Positive at Baseline and Who Had HBV DNA < 400 Copies/mL, Normal ALT, and Seroconversion to HBeAg at Week 72
time frame: Baseline to Week 72
Percentage of Participants Who Had Abnormal ALT at Baseline and Who Had HBV DNA < 400 Copies/mL and ALT Normalized at Week 48
time frame: Baseline to Week 48
Percentage of Participants Who Had Abnormal ALT at Baseline and Who Had HBV DNA < 400 Copies/mL and ALT Normalized at Week 72
time frame: Baseline to Week 72
Percentage of Participants Who Were HBeAG Positive With Abnormal ALT at Baseline, and Who Had HBV DNA < 400 Copies/mL, ALT Normalized, and HBeAg Loss at Week 48
time frame: Baseline to Week 48
Percentage of Participants Who Were HBeAG Positive With Abnormal ALT at Baseline, and Who Had HBV DNA < 400 Copies/mL, ALT Normalized, and HBeAg Loss at Week 72
time frame: Baseline to Week 72
Percentage of Participants Who Were HBeAG Positive With Abnormal ALT at Baseline, and Who Had HBV DNA < 400 Copies/mL, ALT Normalized, and Seroconversion to HBeAg at Week 48
time frame: Baseline to Week 48
Percentage of Participants Who Were HBeAG Positive With Abnormal ALT at Baseline, and Who Had HBV DNA < 400 Copies/mL, ALT Normalized, and Seroconversion to HBeAg at Week 72
time frame: Baseline to Week 72
Number of Participants With at Least a 6% Decrease From Baseline in Spine BMD at Week 48
time frame: Baseline to Week 48
Percent Change From Baseline in Spine BMD at Week 48
time frame: Baseline to Week 48
Percent Change From Baseline in Spine BMD at Week 72
time frame: Baseline to Week 72
Change in Z-score for Spine BMD at Week 48
time frame: Baseline to Week 48
Change in Z-score for Spine BMD at Week 72
time frame: Baseline to Week 72
Percent Change From Baseline in Whole Body BMD at Week 48
time frame: Baseline to Week 48
Percent Change From Baseline in Whole Body BMD at Week 72
time frame: Baseline to Week 72
Change in Z-score for Whole Body BMD at Week 48
time frame: Baseline to Week 48
Change in Z-score for Whole Body BMD at Week 72
time frame: Baseline to Week 72
Number of Participants With Changes in Drug-resistant Mutations at Week 48
time frame: Baseline to Week 48
Number of Participants With Changes in Drug-resistant Mutations at Week 72
time frame: Baseline to Week 72

Eligibility Criteria

Male or female participants from 12 years up to 17 years old.

Inclusion Criteria - 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) - 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) Exclusion Criteria - 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 - Evidence of hepatocellular carcinoma (HCC) - Coinfection with HIV, HCV, or 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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Gilead Sciences.