Completed

Tenofovir Disoproxil Fumarate (Tenofovir DF) Versus Emtricitabine/Tenofovir DF in Subjects Resistant to Lamivudine

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What is being tested

TDF

+ FTC/TDF
+ TDF Placebo
Drug
Who is being recruted

Hepatitis B

From 18 to 75 Years

See all eligibility criteria

How is the trial designed

Treatment Study

Phase 3
Interventional
Study Start: September 2008

See protocol details

Summary

Principal SponsorGilead Sciences
Last updated: March 11, 2016
Sourced from a government-validated database.Claim as a partner
Study start date: September 1, 2008Actual date on which the first participant was enrolled.

The aim of therapy for the treatment of chronic hepatitis B virus (HBV) is to maintain suppression of viral replication to prevent the emergence of complications, which requires long-term therapy. Durable suppression of viral replication is achieved in the treatment of chronic viral diseases by preventing of the emergence of drug-resistant mutations. The clinical guidelines for the management of lamivudine resistant patients are variable. Some recommend switching to another agent without cross-resistance, while others recommend adding on another agent without cross-resistance. Limited clinical data exists to demonstrate whether tenofovir disoproxil fumarate (tenofovir DF; TDF) is an effective monotherapy for lamivudine resistant patients or if it should be used as part of a combination therapy regimen. This study is designed to evaluate the effectiveness, safety, and tolerability of tenofovir DF monotherapy versus emtricitabine (FTC)/tenofovir DF combination therapy in participants with chronic HBV with lamivudine resistance (presence of the rtM204I/V mutation with or without the rtL180M mutation) over a 240-week period. Participants in this study must be receiving lamivudine treatment at the time of enrollment.

Official TitleA Phase 3b, Randomized, Double-Blind, Double-Dummy Study Evaluating the Antiviral Efficacy, Safety, and Tolerability of Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus Emtricitabine Plus Tenofovir DF Fixed-Dose Combination Therapy in Subjects With Chronic Hepatitis B Who Are Resistant to Lamivudine 
Principal SponsorGilead Sciences
Last updated: March 11, 2016
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
280 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are placed into groups randomly, like flipping a coin. This ensures that the study is fair and unbiased, making the results more reliable. By assigning participants by chance, researchers can better compare treatments without external influences.

Other Ways to Assign Participants
Non-randomized allocation: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.
None (Single-arm trial): If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment: Everyone gets the same treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Sequential assignment: Participants receive treatments one after another in a specific order, possibly based on individual responses.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Neither participants nor researchers know who is receiving which treatment. This is the most rigorous way to reduce bias, ensuring that expectations do not influence the results.

Other Ways to Mask Information
Open-label: Everyone knows which treatment is being given.
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
From 18 to 75 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Hepatitis B
Criteria

Inclusion Criteria * Chronic HBV infection, defined as positive serum HBsAg for at least 6 months * 18 through 75 years of age, inclusive * HBV DNA ≥ 10\^3 IU/mL * Receiving treatment with lamivudine with confirmation of HBV reverse transcriptase mutation(s) known to confer resistance to lamivudine (rtM204I/V with or without rtL180M) by central laboratory assessment prior to randomization; adefovir dipivoxil treatment of ≤ 48 weeks at the time of screening (inclusive of combination adefovir dipivoxil + lamivudine at entry) was allowed * Willing and able to provide written informed consent * Negative serum pregnancy test (for females of childbearing potential only) * Calculated creatinine clearance ≥ 50 mL/min * Hemoglobin ≥ 10 g/dL * Neutrophils ≥ 1000 /mm\^3 * No prior oral HBV therapy with approved nucleotide and/or nucleoside therapy or other investigational agents for HBV infection other than lamivudine or adefovir dipivoxil Exclusion Criteria * 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 not willing to use an effective method of contraception during the study * Alanine aminotransferase (ALT) ≥ 10 × the upper limit of the normal range (ULN) * Decompensated liver disease * Interferon or pegylated interferon therapy within 6 months of the screening visit * Alpha fetoprotein \> 50 ng/mL * Evidence of hepatocellular carcinoma * Coinfection with hepatitis C virus, HIV, or hepatitis D virus * Significant renal, cardiovascular, pulmonary, or neurological disease * Received solid organ or bone marrow transplantation * Receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion * Proximal tubulopathy * Known hypersensitivity to the study drugs, the metabolites or formulation excipients

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
TDF plus placebo to match FTC/TDF
Group II
Experimental
FTC/TDF plus placebo to match TDF
Study Objectives
Primary Objectives

Secondary Objectives

Normal ALT was defined as having a value less than or equal to the ULN. The ULN was 43 U/L for males and 34 U/L for females aged 18 to \< 69, and 35 U/L for males and 32 U/L for females aged ≥ 69.

The percentage of participants who were HBeAg positive at baseline and who had HBeAg Loss at the given time point was summarized. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative.

The percentage of participants who were HBeAg positive at baseline and who had seroconversion to anti-HBe at the given time point was summarized. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive.

The percentage of participants with HBsAg Loss at the given time point was summarized. Loss of HBsAg was defined as change of detectable HBsAg from positive to negative.

The percentage of participants with seroconversion to anti-HBs at the given time point was summarized. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive.

The percentage of participants with virologic breakthrough at the given time point was summarized. Virologic breakthrough was defined as having two consecutive 1.0 log10 or greater increases in serum HBV DNA from on-treatment nadir, or two consecutive HBV DNA values ≥ 400 copies/mL after being \< 400 copies/mL.

BMD is calculated as grams per cubic centimeter (g/cm\^2); the mean (SD) percentage change is presented.

BMD is calculated as g/cm\^2; the mean (SD) percentage change is presented.

The development of DRMs was summarized, either as development of new DRMs or enrichment of existing DRMs.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 71 locations
Suspended
Unknown FacilityBradenton, United StatesSee the location
Suspended
Unknown FacilityFlushing, United States
Suspended
Unknown FacilityPhiladelphia, United States
Suspended
Unknown FacilityInnsbruck, Austria
Completed71 Study Centers