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)

NCT ID: NCT00507507

Last Updated: 2015-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2012-08-31

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.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tenofovir DF

Participants were randomized to receive tenofovir DF plus placebo to match FTC once daily.

Group Type: EXPERIMENTAL

Tenofovir DF

Intervention Type: DRUG

Tenofovir disoproxil fumarate (tenofovir DF) 300 mg tablet taken orally once daily

Placebo

Intervention Type: DRUG

Placebo to match FTC taken once daily

FTC+Tenofovir DF

Participants were randomized to receive FTC plus tenofovir DF once daily.

Group Type: EXPERIMENTAL

Tenofovir DF

Intervention Type: DRUG

Tenofovir disoproxil fumarate (tenofovir DF) 300 mg tablet taken orally once daily

FTC

Intervention Type: DRUG

Emtricitabine (FTC) 200 mg capsule taken orally once daily

Interventions

Tenofovir DF

Tenofovir disoproxil fumarate (tenofovir DF) 300 mg tablet taken orally once daily

Intervention Type: DRUG

FTC

Emtricitabine (FTC) 200 mg capsule taken orally once daily

Intervention Type: DRUG

Placebo

Placebo to match FTC taken once daily

Intervention Type: DRUG

Other Intervention Names

Viread®; Emtriva®

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Los Angeles, California, United States

San Diego, California, United States

San Francisco, California, United States

Miami, Florida, United States

Detroit, Michigan, United States

Manhasset, New York, United States

New York, New York, United States

New York, New York, United States

Germantown, Tennessee, United States

Seattle, Washington, United States

Camperdown, New South Wales, Australia

Westmead, New South Wales, Australia

Heidelburg, Victoria, Australia

Melbourne, Victoria, Australia

Calgary, Alberta, Canada

Vancouver, British Columbia, Canada

Toronto, Ontario, Canada

Lille, , France

Lyon, , France

Strasbourg, , France

Berlin, , Germany

Berlin, , Germany

Düsseldorf, , Germany

Frankfurt, , Germany

Hamburg, , Germany

Hanover, , Germany

Heidelberg, , Germany

Herne, , Germany

Mainz, , Germany

Pokfulam, , Hong Kong

Shatin, , Hong Kong

Tai Po, , Hong Kong

Grafton, Auckland, New Zealand

Hamilton, , New Zealand

Bydgoszcz, , Poland

Chorzów, , Poland

Warsaw, , Poland

Singapore, , Singapore

Singapore, , Singapore

Kaohsiung City, , Taiwan

Kaoshiung, , Taiwan

Tainan City, , Taiwan

Taipei, , Taiwan

London, , United Kingdom

Sheffield, , United Kingdom

Countries

United States; Australia; Canada; France; Germany; Hong Kong; New Zealand; Poland; Singapore; Taiwan; United Kingdom

Other Identifiers

GS-US-203-0101

Identifier Type: -

Identifier Source: org_study_id