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)
Information source: Gilead Sciences
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic Hepatitis B
Intervention: Tenofovir DF (Drug); FTC (Drug); Placebo (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Gilead Sciences
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.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192
Secondary outcome: Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192 Change From Baseline in HBV DNA at Week 48 Change From Baseline in HBV DNA at Week 96 Change From Baseline in HBV DNA at Week 144 Change From Baseline in HBV DNA at Week 192 Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192 Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192 Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192 Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192 Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192 Occurrence of HBV Resistance Mutations
Eligibility
Minimum age: 18 Years.
Maximum age: 69 Years.
Gender(s): Both.
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
Locations and Contacts
Lille 59037, France
Lyon 69288, France
Strasbourg 67091, France
Berlin 10969, Germany
Berlin 13353, Germany
Duesseldorf 40237, Germany
Frankfurt 60590, Germany
Hamburg 20251, Germany
Hannover 30623, Germany
Heidelberg 69120, Germany
Herne 44623, Germany
Mainz 55131, Germany
Pokfulam, Hong Kong
Shatin, Hong Kong
Tai Po, Hong Kong
Hamilton, New Zealand
Bydgoszcz 85-030, Poland
Chorzow 41-500, Poland
Warszawa 01-201, Poland
Singapore 119074, Singapore
Singapore 529889, Singapore
Kaohsiung 807, Taiwan
Kaoshiung 833, Taiwan
Tainan 107, Taiwan
Taipei, Taiwan
London NW3 2QG, United Kingdom
Sheffield S10 2JF, United Kingdom
Calgary, Alberta T2N4N1, Canada
Grafton, Auckland 1150, New Zealand
Vancouver, British Columbia V5Z1H2, Canada
Los Angeles, California 90048, United States
San Diego, California 92115, United States
San Francisco, California 11355, United States
Miami, Florida 33136, United States
Detroit, Michigan 48202, United States
Camperdown, New South Wales 2050, Australia
Westmead, New South Wales 2145, Australia
Manhasset, New York 11030, United States
New York, New York 10021, United States
New York, New York 10029-6574, United States
Toronto, Ontario M5G 2C4, Canada
Germantown, Tennessee 38138, United States
Heidelburg, Victoria 3081, Australia
Melbourne, Victoria 3004, Australia
Seattle, Washington 98111, United States
Additional Information
Starting date: September 2007
Last updated: July 7, 2015
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