Overview

This trial is active, not recruiting.

Condition chronic hepatitis b
Treatments tdf, adv, tdf placebo, adv placebo, ftc/tdf
Phase phase 3
Sponsor Gilead Sciences
Start date June 2005
End date May 2007
Trial size 266 participants
Trial identifier NCT00116805, GS-US-174-0103

Summary

This study is designed to evaluate the safety and antiviral activity of tenofovir disoproxil fumarate (TDF, tenofovir DF) compared to adefovir dipivoxil (ADV) for the treatment of HBeAg-positive chronic hepatitis B. Participants will receive either TDF or the approved hepatitis B therapy ADV. After 48 weeks all participants will be switched to open-label TDF.

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, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
TDF plus placebo to match ADV (double-blind period), followed by TDF (open-label period). Participants may add FTC (as part of FTC/TDF fixed dose combination [FDC] tablet) to their treatment regimen in the open-label period.
tdf Viread®
TDF 300 mg tablet administered orally once daily
adv placebo
Placebo to match ADV administered orally once daily
ftc/tdf Truvada®
Emtricitabine (FTC) 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet administered orally once daily
(Active Comparator)
ADV plus placebo to match TDF (double-blind period), followed by TDF (open-label period). Participants may add FTC (as part of FTC/TDF FDC tablet) to their treatment regimen in the open-label period.
tdf Viread®
TDF 300 mg tablet administered orally once daily
adv Hepsera®
ADV 10 mg tablet administered orally once daily
tdf placebo
Placebo to match TDF administered orally once daily
ftc/tdf Truvada®
Emtricitabine (FTC) 200 mg/TDF 300 mg fixed-dose combination (FDC) tablet administered orally once daily

Primary Outcomes

Measure
Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48
time frame: Baseline; Week 48

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 < 400 Copies/mL at Week 96
time frame: Week 96
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384
time frame: Weeks 144, 192, 240, 288, 336, and 384
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, and 384
time frame: Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, and 384
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, and 384
time frame: Week 48; Weeks 96, 144, 192, 240, 288, 336, and 384
Percentage of Participants With Histological Response at Week 48
time frame: Baseline; Week 48
Percentage of Participants With Histological Response at Week 240
time frame: Baseline; Week 240
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48
time frame: Baseline; Week 48
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240
time frame: Baseline; Week 240
Ranked Assessment of Necroinflammation and Fibrosis at Week 48
time frame: Baseline; Week 48
Ranked Assessment of Necroinflammation and Fibrosis at Week 240
time frame: Baseline; Week 240
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48
time frame: Baseline; Week 48
Percentage of Participants With ALT Normalization at Week 96
time frame: Baseline; Week 96
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384
time frame: Baseline; Weeks 144, 192, 240, 288, 336, and 384
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, and 384
time frame: Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, and 384
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, and 384
time frame: Week 48; Weeks 96, 144, 192, 240, 288, 336, and 384
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48
time frame: Baseline; Week 48
Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96
time frame: Baseline to Week 96
Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48
time frame: Week 48
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96
time frame: Baseline; Weeks 96, 144, 192, 240, 288, 336, and 384
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, and 384
time frame: Baseline; Weeks 144, 192, 240, 288, 336, and 384
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)
time frame: Baseline; Week 48
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)
time frame: Baseline; Weeks 49 to 95
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)
time frame: Baseline; Weeks 97 to 144
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)
time frame: Baseline; Weeks 145 to 192
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)
time frame: Baseline; Weeks 193 to 240
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)
time frame: Baseline; Weeks 241 to 288
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)
time frame: Baseline; Weeks 289 to 336
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)
time frame: Baseline; Weeks 337 to 384

Eligibility Criteria

Male or female participants from 18 years up to 69 years old.

Inclusion Criteria: A patient must meet all of the following inclusion criteria to be eligible for participation in this study: - Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B s-antigen (HBsAg) for more than 6 months - 18 through 69 years of age, inclusive - Active hepatitis B e-antigen (HBeAg) positive chronic HBV infection, with all of the following: - HBeAg positive at screening - Alanine aminotransferase (ALT) levels > 2 × ULN and ≤ 10 × the upper limit of the normal range (ULN) - Serum HBV DNA > 1 million copies/mL at screening - creatinine clearance ≥ 70 mL/min - hemoglobin ≥ 8 g/dL - neutrophils ≥ 1,000 /mL - Knodell necroinflammatory score ≥ 3 and a Knodell fibrosis score < 4; however, up to 96 patients with cirrhosis, ie, a Knodell fibrosis score equal to 4, will be eligible for enrollment - Negative serum β-human chorionic gonadotropin (hCG) - Nucleotide naïve, ie, no prior nucleotide (TDF or ADV) therapy for > 12 weeks - Nucleoside naïve, ie, no prior nucleoside (any nucleoside) therapy for > 12 weeks - Willing and able to provide written informed consent - Liver biopsy performed within 6 months of baseline and has readable biopsy slides or agrees to have a biopsy performed prior to baseline Exclusion Criteria: A patient who meets any of the following exclusion criteria is not to be enrolled in this study: - 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 unwilling to use an effective method of contraception during the study; for males, condoms should be used and for females, a barrier contraception method should be used - Decompensated liver disease defined as conjugated bilirubin > 1.5 x ULN, prothrombin time (PT) > 1.5 x ULN, platelets < 75,000/mL, serum albumin < 3.0 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage) - Received any nucleoside, nucleotide (TDF or ADV) or interferon (pegylated or not) therapy within 6 months prior to the pre-treatment biopsy - Evidence of hepatocellular carcinoma (HCC), ie, α-fetoprotein >50 ng/mL - Coinfection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis delta virus (HDV) - Significant renal, cardiovascular, pulmonary, or neurological disease - Received solid organ or bone marrow transplantation - Is currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion - Has proximal tubulopathy

Additional Information

Official title A Randomized, Double-Blind, Controlled Evaluation of Tenofovir DF Versus Adefovir Dipivoxil for the Treatment of HBeAg Positive Chronic Hepatitis B
Description Efficacy of TDF versus ADV will be evaluated for histologic improvement, reductions in serum HBV DNA, changes in liver enzymes, and the generation of antibody to the virus. Safety will be assessed by evaluating adverse events, laboratory abnormalities and the development of drug-resistant mutations. After 48 weeks, all participants will receive open-label TDF, and the efficacy and safety of TDF will be monitored for the remainder of the study.
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by Gilead Sciences.