A Study to Compare Tenofovir DF Versus the Combination of Emtricitabine Plus Tenofovir DF for the Treatment of Chronic Hepatitis B in Patients With Normal Alanine Aminotransferase (ALT)

Gilead Sciences126 enrolled

Overview

The main objective of the study was to evaluate the antiviral activity of tenofovir disoproxil fumarate (tenofovir DF) monotherapy versus emtricitabine (FTC) plus tenofovir DF combination therapy for the treatment of chronic hepatitis B (HBV) in participants in the immune tolerant phase of HBV infection. The efficacy of tenofovir DF monotherapy versus FTC plus tenofovir DF combination therapy was evaluated for suppression of the virus (decrease in HBV DNA), serological response (generation of antibodies to the virus), biochemical response (changes in liver enzymes), and the development of drug-resistant mutations. The safety and tolerability of both tenofovir DF monotherapy and FTC plus tenofovir DF were evaluated by routine monitoring for adverse events and changes in laboratory parameters. Participants were randomized in a 1:1 ratio to receive tenofovir DF monotherapy or FTC plus tenofovir DF. All subjects were to continue on blinded study medication until the last subject reached Week 192. Participants who permanently discontinued study drug (on or before Week 192) were followed for a 24-week treatment-free follow-up period, or until initiation of alternative HBV therapy, whichever occurred first. Subjects who discontinued study drug on or after Week 48 because of hepatitis B surface antigen (HBsAg) loss or seroconversion to antibody to hepatitis B surface antigen (anti-HBs), however, were to have returned for their regularly scheduled through Week 192 and every 16 weeks thereafter until the last subject reached Week 192.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

126

Conditions

Chronic Hepatitis B

Eligibility

Sex: ALLMin age: 18 YearsMax age: 69 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Chronic HBV infection, defined as positive serum HBsAg for at least 6 months or HBsAg positive \> 3 months and positive for immunoglobulin G antibody against hepatitis B core antigen * 18 through 69 years of age, inclusive * Hepatitis B e antigen (HBeAg) positive * HBV DNA ≥ 10\^8 copies/mL * ALT ≤ the upper limit of the normal range (ULN) * Willing and able to provide written informed consent * Negative serum beta-human chorionic gonadotropin (for females of childbearing potential only) * Calculated creatinine clearance ≥ 70 mL/min * Hemoglobin ≥ 10 g/dL * Neutrophils ≥ 1,500/mm\^3 * No prior oral HBV therapy (eg, nucleotide and/or nucleoside therapy or other investigational agents for HBV infection) Exclusion Criteria: * Pregnant women, women who were breast feeding, or who believed they may have wished to become pregnant during the course of the study * Males and females of reproductive potential unwilling to use an effective method of contraception during the study * Decompensated liver disease defined as direct (conjugated) bilirubin \> 1.2 x ULN, prothrombin time \> 1.2 x ULN, platelets \< 150,000/mm\^3, serum albumin \< 3.5 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, or variceal hemorrhage) * Received interferon (pegylated or not) therapy within 6 months of the screening visit * Alpha-fetoprotein \> 50 ng/mL * Evidence of hepatocellular carcinoma * Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus * Significant renal, cardiovascular, pulmonary, or neurological disease * Received solid organ or bone marrow transplantation * Was currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion * Had proximal tubulopathy * Known hypersensitivity to the study drugs, the metabolites, or formulation excipients

Outcomes

Primary Outcomes

Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192

The percentage of participants with HBV DNA \< 400 copies/mL at Week 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.

Time frame: Week 192

Secondary Outcomes

Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144

The percentage of participants with HBV DNA \< 400 copies/mL at Weeks 48, 96, and 144 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.

Time frame: Weeks 48, 96, and 144

Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192

The percentage of participants with HBV DNA \< 169 copies/mL at Weeks 48, 96, 144, and 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation.

Time frame: Weeks 48, 96, 144, and 192

Change From Baseline in HBV DNA at Week 48

The change from baseline in HBV DNA at Week 48 was analyzed.

Time frame: Baseline to Week 48

Change From Baseline in HBV DNA at Week 96

The change from baseline in HBV DNA at Week 96 was analyzed.

Time frame: Baseline to Week 96

Change From Baseline in HBV DNA at Week 144

The change from baseline in HBV DNA at Week 144 was analyzed.

Time frame: Baseline to Week 144

Change From Baseline in HBV DNA at Week 192

The change from baseline in HBV DNA at Week 192 was analyzed.

Time frame: Baseline to Week 192

Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192

Range of normal ALT was 6 to 34 U/L for females, 6 to 43 U/L for males. Participants with missing data were considered to have failed to achieve the criteria for evaluation.

Time frame: Weeks 48, 96, 144, and 192

Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192

The number of participants with HBeAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. No statistical analysis is presented for Week 48 because no participants met the criteria at that time point.

Time frame: Weeks 48, 96, 144, and 192

Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192

The number of participants with seroconversion to anti-HBe at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive. No statistical analysis is presented for Week 48 because no participants met the criteria at that time point.

Time frame: Weeks 48, 96, 144, and 192

Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192

The number of participants with HBsAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBsAg was defined as change of detectable HBsAg from positive to negative.

Time frame: Weeks 48, 96, 144, and 192

Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192

The number of participants with seroconversion to anti-HBs at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive.

Time frame: Weeks 48, 96, 144, and 192

Occurrence of HBV Resistance Mutations

The development of HBV resistance mutations (occurrence of conserved site changes and/or polymorphic site changes) was analyzed for the overall study period (through Week 192).

Time frame: Baseline to Week 192

A Study to Compare Tenofovir DF Versus the Combination of Emtricitabine Plus Tenofovir DF for the Treatment of Chronic Hepatitis B in Patients With Normal Alanine Aminotransferase (ALT)

Overview

Conditions

Interventions

Eligibility

Locations (45)

Outcomes

Primary Outcomes

Secondary Outcomes