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Trial registered on ANZCTR


Registration number
ACTRN12607000371493
Ethics application status
Not yet submitted
Date submitted
10/07/2007
Date registered
13/07/2007
Date last updated
13/07/2007
Type of registration
Retrospectively registered

Titles & IDs
Public 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
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] 389 0
Gilead: 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 1951 0
Condition category
Condition code
Inflammatory and Immune System 2046 2046 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The current study will be looking at the efficacy, safety and tolerability of tenofovir DF monotherapy versus the once-daily combination of tenofovir DF plus emtricitabine in patients who have chronic Hepatitis B Virus [Hepatitis B e Antigen (HBeAg) negative or positive disease]. Subjects will be randomized in a 1:1 ratio to treatment arms A or B. Tenofovir DF 300 mg will be provided open-label while emtricitabine 200 mg will be provided in a blinded fashion: Treatment B: Open label tenofovir DF 300 mg once daily +emtricitabine 200 mg once daily. Subjects will be instructed to take 1 pill from each bottle once daily: one tablet (open label tenofovir DF) and one capsule (emtricitabine 200 mg). All subjects will continue on study medication until Week 48. At Week 48, Gilead Sciences will provide open label tenofovir DF 300 mg for study subjects in countries where the drug is not commercially available, until such access is available. Subjects who wish to discontinue therapy will be followed off treatment for 24 weeks or until the initiation of alternate commercial therapy.
Intervention code [1] 1885 0
Treatment: Drugs
Comparator / control treatment
Treatment A: Open label tenofovir DF 300 mg once daily + emtricitabine placebo once daily. Subjects will be instructed to take 1 pill from each bottle once daily: one tablet (open label tenofovir DF) and one capsule (matching placebo).
Control group
Active

Outcomes
Primary outcome [1] 2875 0
The primary objective of this study is to compare the antiviral efficacy against hepatitis B virus of tenofovir DF monotherapy versus tenofovir DF plus emtricitabine combination therapy. The parameter being virological suppression, i.e., HBV DNA < Lower Limit of Quantitation (LLOQ) at Week 48.
Timepoint [1] 2875 0
Assessments will take place at baseline, week 4, 8, 16, 24, 32, 40 and 48 (or end of treatment). Subjects who have received at least one dose of study drug and permanently discontinue study drug will be followed for 24 weeks off treatment or up to initiation of active treatment, which ever occurs first. The follow-up evaluations will take place every 4 weeks for the 24 week follow-up period.
Secondary outcome [1] 4843 0
To evaluate the safety and tolerability of tenofovir DF monotherapy versus tenofovir DF plus emtricitabine combination therapy
Timepoint [1] 4843 0
Secondary objectives will be measured by the change from baseline in log10 HBV DNA, normal ALT, HBeAg/HBsAg loss and seroconversion, development of drug resistant mutations and the time-weighted average change from baseline (DAVG)48 in log10 HBV DNA through Week 48. The null and alternative hypotheses are as follows: H0: There is no difference between treatment groups in the proportion of subjects with HBV DNA below lower limit of quantification (LLOQ) at Week 48. Ha: There is a difference between treatment groups in the proportion of subjects with HBV DNA below lower limit of quantification (LLOQ) at Week 48.
Assessments will take place at baseline, week 4, 8, 16, 24, 32, 40 and 48 (or end of treatment). Subjects who have received at least one dose of study drug and permanently discontinue study drug will be followed for 24 weeks off treatment or up to initiation of active treatment, which ever occurs first. The follow-up evaluations will take place every 4 weeks for the 24 week follow-up period.
Secondary outcome [2] 4844 0
To evaluate the biochemical and serological response to tenofovir DF monotherapy versus tenofovir DF plus emtricitabine combination therapy.
Timepoint [2] 4844 0
Secondary objectives will be measured by the change from baseline in log10 HBV DNA, normal ALT, HBeAg/HBsAg loss and seroconversion, development of drug resistant mutations and the time-weighted average change from baseline (DAVG)48 in log10 HBV DNA through Week 48. The null and alternative hypotheses are as follows: H0: There is no difference between treatment groups in the proportion of subjects with HBV DNA below lower limit of quantification (LLOQ) at Week 48. Ha: There is a difference between treatment groups in the proportion of subjects with HBV DNA below lower limit of quantification (LLOQ) at Week 48.
Assessments will take place at baseline, week 4, 8, 16, 24, 32, 40 and 48 (or end of treatment). Subjects who have received at least one dose of study drug and permanently discontinue study drug will be followed for 24 weeks off treatment or up to initiation of active treatment, which ever occurs first. The follow-up evaluations will take place every 4 weeks for the 24 week follow-up period.
Secondary outcome [3] 4845 0
To compare the incidence of drug resistant mutations between treatment arms.
Timepoint [3] 4845 0
Secondary objectives will be measured by the change from baseline in log10 HBV DNA, normal ALT, HBeAg/HBsAg loss and seroconversion, development of drug resistant mutations and the time-weighted average change from baseline (DAVG)48 in log10 HBV DNA through Week 48. The null and alternative hypotheses are as follows: H0: There is no difference between treatment groups in the proportion of subjects with HBV DNA below lower limit of quantification (LLOQ) at Week 48. Ha: There is a difference between treatment groups in the proportion of subjects with HBV DNA below lower limit of quantification (LLOQ) at Week 48.
Assessments will take place at baseline, week 4, 8, 16, 24, 32, 40 and 48 (or end of treatment). Subjects who have received at least one dose of study drug and permanently discontinue study drug will be followed for 24 weeks off treatment or up to initiation of active treatment, which ever occurs first. The follow-up evaluations will take place every 4 weeks for the 24 week follow-up period.

Eligibility
Key inclusion criteria
To be eligible for participation, at screening subjects with chronic Hepatitis B Virus (HBV) infection [Hepatitis B Surface Antigen (HBsAg) > 6 months or HBsAg positive > 3 months and negative for Immunoglobulin M (IgM), Antibodies to Hepatitis B Core Antigen (anti-HBc) and positive for Immunoglobin G (IgG) anti-HBc], HBV DNA levels > or = 10^8 copies/mL, Alanine Transferase (ALT) levels > or = Upper Limit of Normal (ULN), creatinine clearance > or = 70 mL/min, alpha-fetoprotein < 50 ng/mL.
Minimum age
18 Years
Maximum age
69 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects must be naïve to oral HBV therapy and without serological evidence of co-infection with Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), or Hepatitis D Virus (HDV). Previous treatment with interferon must have ended at least 6 months prior to the screening visit. Subjects with decompensated liver disease as well as pregnant or breast-feeding females will be excluded from the study. Regular visits will involve the review of vital signs and collection of blood to perform routine lab tests of serum chemistry, liver tests, hematology and HBV DNA. Tests specific to HBV and a physical examination will be done at specific visits. A sample of urine will also be collected at each visit for urinalysis and a urine pregnancy test will be requested for females of child bearing potential.

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)
At randomisation (Visit 2/Baseline visit), the investigator or designee will phone Interactive Voice Recognition System (IVRS) which will assign a randomization number and drug kit for the patient
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
The following people will be blinded for this trial: the people receiving the treatment/s (subjects), the people administering the treatment/s (clinician), the people assessing the outcomes (assessor) and the people analysing the results/data (data analyst).
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/06/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final

Funding & Sponsors
Funding source category [1] 2189 0
Commercial sector/Industry
Name [1] 2189 0
Gilead
Country [1] 2189 0
Primary sponsor type
Commercial sector/Industry
Name
Gilead
Address
Country
Secondary sponsor category [1] 1975 0
None
Name [1] 1975 0
None
Address [1] 1975 0
Country [1] 1975 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 3986 0
Austin Health, Department of Gastroenterology and Hepatology
Ethics committee address [1] 3986 0
Ethics committee country [1] 3986 0
Australia
Date submitted for ethics approval [1] 3986 0
Approval date [1] 3986 0
Ethics approval number [1] 3986 0
Ethics committee name [2] 3987 0
Westmead Hospital, Storr Liver Unit
Ethics committee address [2] 3987 0
Ethics committee country [2] 3987 0
Australia
Date submitted for ethics approval [2] 3987 0
Approval date [2] 3987 0
Ethics approval number [2] 3987 0
Ethics committee name [3] 3988 0
The Alfred Hospital, Department of Gastroenterology
Ethics committee address [3] 3988 0
Ethics committee country [3] 3988 0
Australia
Date submitted for ethics approval [3] 3988 0
Approval date [3] 3988 0
Ethics approval number [3] 3988 0
Ethics committee name [4] 3989 0
Royal Prince Alfred Hospital, AW Morrow Gastroenterology and Liver Centre
Ethics committee address [4] 3989 0
Ethics committee country [4] 3989 0
Australia
Date submitted for ethics approval [4] 3989 0
Approval date [4] 3989 0
Ethics approval number [4] 3989 0

Summary
Brief summary
The aim of treatment for HBV is to suppress viral replication and to prevent the emergence of complications and to ultimately clear the virus and produce seroconversion with Antibodies to Hepatitis Bs (anti-HBs). Achieving this goal requires long-term therapy. Monotherapies have found to be insufficient in most chronic viral diseases. Analysis of the primary endpoint will be summarised by the proportion of subjects meeting the endpoint for each treatment arm (the primary endpoint is to supress the viral load below the limit of detection by week 48).
The study hypothesis is that there will be a difference between treatment groups in the proportion of subjects with HBV DNA below the detectable level at week 48.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27699 0
Address 27699 0
Country 27699 0
Phone 27699 0
Fax 27699 0
Email 27699 0
Contact person for public queries
Name 11074 0
Alison Lai
Address 11074 0
ICON Clinical Research
Suite 201
Level 2
2-4 Lyon Park Road
North Ryde NSW 2113
Country 11074 0
Australia
Phone 11074 0
+61 2 98593915
Fax 11074 0
Email 11074 0
[email protected]
Contact person for scientific queries
Name 2002 0
Alison Lai
Address 2002 0
ICON Clinical Research
Suite 201
Level 2
2-4 Lyon Park Road
North Ryde NSW 2113
Country 2002 0
Australia
Phone 2002 0
+61 2 98593915
Fax 2002 0
Email 2002 0
[email protected]

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