Chronic Hepatitis BPhase 2NCT00507507
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)
A Phase 2 study testing Tenofovir DF and FTC in people with Chronic Hepatitis B, run by Gilead Sciences at 45 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Tenofovir DF and FTC
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 126 participants
- Where
- 45 sitesin 11 countries
- Study dates
- Sep 2007to Aug 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
45 sites in 11 countries.
45 sites in 11 countries
United States10 sites
Study site
Detroit, Michigan, 48202
Study site
Germantown, Tennessee, 38138
Study site
Los Angeles, California, 90048
Study site
Manhasset, New York, 11030
Study site
Miami, Florida, 33136
Study site
New York, New York, 10021
Study site
New York, New York, 10029-6574
Study site
San Diego, California, 92115
Study site
San Francisco, California, 11355
Study site
Seattle, Washington, 98111
Germany9 sites
Study site
Berlin, 10969
Study site
Berlin, 13353
Study site
Düsseldorf, 40237
Study site
Frankfurt, 60590
Study site
Hamburg, 20251
Study site
Hanover, 30623
Study site
Heidelberg, 69120
Study site
Herne, 44623
Study site
Mainz, 55131
Australia4 sites
Study site
Camperdown, New South Wales, 2050
Study site
Heidelburg, Victoria, 3081
Study site
Melbourne, Victoria, 3004
Study site
Westmead, New South Wales, 2145
Taiwan4 sites
Study site
Kaohsiung City, 807
Study site
Kaoshiung, 833
Study site
Tainan, 107
Study site
Taipei
Canada3 sites
Study site
Calgary, Alberta, T2N4N1
Study site
Toronto, Ontario, M5G 2C4
Study site
Vancouver, British Columbia, V5Z1H2
France3 sites
Study site
Lille, 59037
Study site
Lyon, 69288
Study site
Strasbourg, 67091
Poland3 sites
Study site
Bydgoszcz, 85-030
Study site
Chorzów, 41-500
Study site
Warsaw, 01-201
United Kingdom2 sites
Study site
London, NW3 2QG
Study site
Sheffield, S10 2JF
About this study
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
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
- Being tested
- Tenofovir DF, FTC, Placebo
- Keywords
- tenofovir, monotherapy, emtricitabine, combination, hepatitis B
- Medical subject headings
- Hepatitis B, Chronic, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir DFDrug
Also called Viread®
Tenofovir disoproxil fumarate (tenofovir DF) 300 mg tablet taken orally once daily
FTCDrug
Also called Emtriva®
Emtricitabine (FTC) 200 mg capsule taken orally once daily
PlaceboDrug
Placebo to match FTC taken once daily
| Study group | Role | What they receive |
|---|---|---|
| Tenofovir DF | Experimental | Participants were randomized to receive tenofovir DF plus placebo to match FTC once daily. Receives: Drug: Tenofovir DF; Drug: Placebo |
| FTC+Tenofovir DF | Experimental | Participants were randomized to receive FTC plus tenofovir DF once daily. Receives: Drug: Tenofovir DF; Drug: FTC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 192
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: Baseline to Week 192
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2007 (estimated)
- Study startSep 2007
- Primary completionFeb 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00507507
- Sponsor's protocol ID
- GS-US-203-0101
- Status last verified
- Jul 2015
- First submitted
- 25 Jul 2007
- Last updated
- 17 Jul 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00507507
- Acronym / sponsor ID
- GS-US-203-0101
- Conditions
- Chronic Hepatitis B
- Keywords
- tenofovir, monotherapy, emtricitabine, combination, hepatitis B
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 126 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Sep 2007
- Primary completion
- Feb 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 26 Jul 2007 (estimated)
- Results
- Posted 8 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tenofovir DF | Experimental | Drug: Tenofovir DF, Drug: PlaceboParticipants were randomized to receive tenofovir DF plus placebo to match FTC once daily. |
| FTC+Tenofovir DF | Experimental | Drug: Tenofovir DF, Drug: FTCParticipants were randomized to receive FTC plus tenofovir DF once daily. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir DFAlso: Viread®Tenofovir disoproxil fumarate (tenofovir DF) 300 mg tablet taken orally once daily | Drug | FTC+Tenofovir DF, Tenofovir DF |
| FTCAlso: Emtriva®Emtricitabine (FTC) 200 mg capsule taken orally once daily | Drug | FTC+Tenofovir DF |
| PlaceboPlacebo to match FTC taken once daily | Drug | Tenofovir DF |
Primary outcome
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192
Time frame: 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.
12 secondary outcomes
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144
Time frame: Weeks 48, 96, and 144
Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192
Time frame: Weeks 48, 96, 144, and 192
Change From Baseline in HBV DNA at Week 48
Time frame: Baseline to Week 48
Change From Baseline in HBV DNA at Week 96
Time frame: Baseline to Week 96
Change From Baseline in HBV DNA at Week 144
Time frame: Baseline to Week 144
Change From Baseline in HBV DNA at Week 192
Time frame: Baseline to Week 192
Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192
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
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
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
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
Time frame: Weeks 48, 96, 144, and 192
Occurrence of HBV Resistance Mutations
Time frame: Baseline to Week 192
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
45 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tenofovir DF and FTC in people with Chronic Hepatitis B, run by Gilead Sciences at 45 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, Germany, Australia, Taiwan, Canada and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192 (time frame: Week 192). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2015.