Clinical trial NCT00507507: 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)
Official title: A Randomized, Double-Blind Study Evaluating Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus the Combination of Emtricitabine and Tenofovir DF for the Treatment of Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: tenofovir
monotherapy
emtricitabine
combination
hepatitis B
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2007-07-26
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192
timeFrame: Week 192
Secondary outcomes:
measure: Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144
timeFrame: Weeks 48, 96, and 144
measure: Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192
timeFrame: Weeks 48, 96, 144, and 192
measure: Change From Baseline in HBV DNA at Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in HBV DNA at Week 96
timeFrame: Baseline to Week 96
measure: Change From Baseline in HBV DNA at Week 144
timeFrame: Baseline to Week 144
measure: Change From Baseline in HBV DNA at Week 192
timeFrame: Baseline to Week 192
measure: Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192
timeFrame: Weeks 48, 96, 144, and 192
measure: Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192
timeFrame: Weeks 48, 96, 144, and 192
measure: Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192
timeFrame: Weeks 48, 96, 144, and 192
measure: Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192
timeFrame: Weeks 48, 96, 144, and 192
measure: Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192
timeFrame: Weeks 48, 96, 144, and 192
measure: Occurrence of HBV Resistance Mutations
timeFrame: Baseline to Week 192
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Detroit
country: United States
state: Michigan
city: Manhasset
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Germantown
country: United States
state: Tennessee
city: Seattle
country: United States
state: Washington
city: Camperdown
country: Australia
state: New South Wales
city: Westmead
country: Australia
state: New South Wales
city: Heidelburg
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Toronto
country: Canada
state: Ontario
city: Lille
country: France
city: Lyon
country: France
city: Strasbourg
country: France
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Duesseldorf
country: Germany
city: Frankfurt
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Herne
country: Germany
city: Mainz
country: Germany
city: Pokfulam
country: Hong Kong
city: Shatin
country: Hong Kong
city: Tai Po
country: Hong Kong
city: Grafton
country: New Zealand
state: Auckland
city: Hamilton
country: New Zealand
city: Bydgoszcz
country: Poland
city: Chorzow
country: Poland
city: Warszawa
country: Poland
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Kaohsiung
country: Taiwan
city: Kaoshiung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: London
country: United Kingdom
city: Sheffield
country: United Kingdom
Study officials:
References: