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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00507507




Registration number
NCT00507507
Ethics application status
Date submitted
25/07/2007
Date registered
26/07/2007
Date last updated
17/07/2015

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
GS-US-203-0101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tenofovir DF
Treatment: Drugs - FTC
Treatment: Drugs - Placebo

Experimental: Tenofovir DF - Participants were randomized to receive tenofovir DF plus placebo to match FTC once daily.

Experimental: FTC+Tenofovir DF - Participants were randomized to receive FTC plus tenofovir DF once daily.


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

Treatment: Drugs: FTC
Emtricitabine (FTC) 200 mg capsule taken orally once daily

Treatment: Drugs: Placebo
Placebo to match FTC taken once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Week 192
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Weeks 48, 96, and 144
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Weeks 48, 96, 144, and 192
Secondary outcome [3] 0 0
Change From Baseline in HBV DNA at Week 48 - The change from baseline in HBV DNA at Week 48 was analyzed.
Timepoint [3] 0 0
Baseline to Week 48
Secondary outcome [4] 0 0
Change From Baseline in HBV DNA at Week 96 - The change from baseline in HBV DNA at Week 96 was analyzed.
Timepoint [4] 0 0
Baseline to Week 96
Secondary outcome [5] 0 0
Change From Baseline in HBV DNA at Week 144 - The change from baseline in HBV DNA at Week 144 was analyzed.
Timepoint [5] 0 0
Baseline to Week 144
Secondary outcome [6] 0 0
Change From Baseline in HBV DNA at Week 192 - The change from baseline in HBV DNA at Week 192 was analyzed.
Timepoint [6] 0 0
Baseline to Week 192
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Weeks 48, 96, 144, and 192
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Weeks 48, 96, 144, and 192
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Weeks 48, 96, 144, and 192
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Weeks 48, 96, 144, and 192
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Weeks 48, 96, 144, and 192
Secondary outcome [12] 0 0
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).
Timepoint [12] 0 0
Baseline to Week 192

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
69 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- Westmead
Recruitment hospital [3] 0 0
- Heidelburg
Recruitment hospital [4] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
3081 - Heidelburg
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington
Country [7] 0 0
Canada
State/province [7] 0 0
Alberta
Country [8] 0 0
Canada
State/province [8] 0 0
British Columbia
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
France
State/province [10] 0 0
Lille
Country [11] 0 0
France
State/province [11] 0 0
Lyon
Country [12] 0 0
France
State/province [12] 0 0
Strasbourg
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Germany
State/province [14] 0 0
Duesseldorf
Country [15] 0 0
Germany
State/province [15] 0 0
Frankfurt
Country [16] 0 0
Germany
State/province [16] 0 0
Hamburg
Country [17] 0 0
Germany
State/province [17] 0 0
Hannover
Country [18] 0 0
Germany
State/province [18] 0 0
Heidelberg
Country [19] 0 0
Germany
State/province [19] 0 0
Herne
Country [20] 0 0
Germany
State/province [20] 0 0
Mainz
Country [21] 0 0
Hong Kong
State/province [21] 0 0
Pokfulam
Country [22] 0 0
Hong Kong
State/province [22] 0 0
Shatin
Country [23] 0 0
Hong Kong
State/province [23] 0 0
Tai Po
Country [24] 0 0
New Zealand
State/province [24] 0 0
Auckland
Country [25] 0 0
New Zealand
State/province [25] 0 0
Hamilton
Country [26] 0 0
Poland
State/province [26] 0 0
Bydgoszcz
Country [27] 0 0
Poland
State/province [27] 0 0
Chorzow
Country [28] 0 0
Poland
State/province [28] 0 0
Warszawa
Country [29] 0 0
Singapore
State/province [29] 0 0
Singapore
Country [30] 0 0
Taiwan
State/province [30] 0 0
Kaohsiung
Country [31] 0 0
Taiwan
State/province [31] 0 0
Kaoshiung
Country [32] 0 0
Taiwan
State/province [32] 0 0
Tainan
Country [33] 0 0
Taiwan
State/province [33] 0 0
Taipei
Country [34] 0 0
United Kingdom
State/province [34] 0 0
London
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00507507
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications