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Trial registered on ANZCTR


Trial ID
ACTRN12605000029695
Ethics application status
Approved
Date submitted
22/07/2005
Date registered
22/07/2005
Date last updated
22/07/2005
Type of registration
Prospectively registered

Titles & IDs
Public title
Tenofovir versus Adefovir for the treatment of HBeAg negative chronic hepatitis B
Scientific title
A randomised, phase III, double blind study to evaluate the efficacy and safety of tenofovir DF versus adefovir dipivoxil in the treatment of presumed pre-core mutant chronic hepatitis B to suppress viral replication, amend the course of the disease and decrease morbidity.
Universal Trial Number (UTN)
Trial acronym
GS-US-174-0102
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HBeAg negative Chronic Hepatitis B 92 0
Condition category
Condition code
Inflammatory and Immune System 113 113 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
To compare the efficacy of tenofovir DF 300 mg versus adefovir dipivoxil 10mg for the treatment of presumed pre-core mutany chronic hepatitis B over 48 weeks of treatment
Intervention code [1] 48 0
Treatment: Drugs
Comparator / control treatment
Control group
Placebo

Outcomes
Primary outcome [1] 140 0
The primary efficacy parameter is the proportion of patients treated with tenofovir DF 300mg QD versus adefovir dipivoxil 10 mg QD with a complete response. A complete response is defined as serum HBV DNA levels below 400 copies/mL and histologic improvement defined as at least a 2 point reduction in the Knodell necroinflammatory score without worsening in the Knodell fibrosis score.
Timepoint [1] 140 0
At the end of the 48 week treatment period
Primary outcome [2] 141 0
To compare the safety and tolerability of tenofovir DF 300 mg QD versus adefovir dipivoxil 10mg QD
Timepoint [2] 141 0
Over the 48 week treatment period
Secondary outcome [1] 314 0
To evaluate the incidence of drug-resistant mutations between treatment arms and to compare the virological, serological, biochemical and histologic response of tenofovir DF 300mg QD versus adefovir dipivoxil 10mg QD for the treatment of presumed pre-core mutant chronic hepatitis B.
Timepoint [1] 314 0
Over 48 weeks of treatment.

Eligibility
Key inclusion criteria
Adult patients (18-69 years of age) with presumed pre-core mutant chronic hepatitis B (HBsAg negative and HBsAg positive), HBsAg positive for more than 6 months with serum HBV DNA >10 to the 5 copies /mL, ALT levels >1.5 and less than or equal to 10x ULN and a Knodell necroinflammatory score of greater than or equal to 3 and a Knodell fibrosis score equal to 4 will be eligible for enrollment. However, up to 120 patients with cirrhosis, i.e. knodell fibrosis score equal to 4, will be eligible for enrollment. Patients who have not had a bopisy within 6 months at baseline must agree to undergo a liver biopsy prior to randomisation. No evidence of hepatocellular carcinoma (HCC) ie. fetoptotein < 50 ng/mL at screening. Patients are eligible if they are treatment naive, ie less than 12 weeks of prior nucleoside or nucleotide (adefovir, dipivoxil or tenofovir DF) treatment, or with prior lamivudine experience of any duration. Enrollment of lamivudine experienced patients will be capped at up to 40% of the patient population (ie120 patients). Any previous treatment with nucleosides and nucleotides (eg up to 12 weeks) and interferon (pegylated or not) must have ended at least 6 months prior to the pre-treatment biopsy.
Minimum age
18 Years
Maximum age
69 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients must be without HIV, HCV and HDV infection. Pregnant and breast feeding women will be excluded from the study and patients with decompensated liver disease or a history of decompensated liver disease (ascites, jaundice, encephalopathy or variceal haemorrhage) will be excluded from the study.

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)
A centralised randomisation procedure will be used whereby numbered bottles will be assigned to patients via an interactive voice response system (IVRS) according to the randomisation code
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomly allocated by IVRS; stratified by prior nucleoside exposure and geographic region
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
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)

Funding & Sponsors
Funding source category [1] 155 0
Commercial sector/Industry
Name [1] 155 0
Gilead Sciences Inc
Address [1] 155 0
Country [1] 155 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences Inc
Address
Country
United States of America
Secondary sponsor category [1] 110 0
None
Name [1] 110 0
NA
Address [1] 110 0
Country [1] 110 0

Ethics approval
Ethics application status
Approved

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35963 0
Address 35963 0
Country 35963 0
Phone 35963 0
Fax 35963 0
Email 35963 0
Contact person for public queries
Name 9237 0
A/Prof Paul Desmond
Address 9237 0
Department of Gastroenterolgy
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy VIC 3065
Country 9237 0
Australia
Phone 9237 0
+61 3 92883580
Fax 9237 0
+61 3 92883590
Email 9237 0
desmondpv@svhm.org.au
Contact person for scientific queries
Name 165 0
A/Prof Paul Desmond
Address 165 0
Department of Gastroenterolgy
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy VIC 3065
Country 165 0
Australia
Phone 165 0
+61 3 92883580
Fax 165 0
+61 3 92883590
Email 165 0
desmondpv@svhm.org.au