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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00116805




Registration number
NCT00116805
Ethics application status
Date submitted
30/06/2005
Date registered
1/07/2005
Date last updated
9/03/2017

Titles & IDs
Public title
A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Positive Chronic Hepatitis B
Scientific title
A Randomized, Double-Blind, Controlled Evaluation of Tenofovir DF Versus Adefovir Dipivoxil for the Treatment of HBeAg Positive Chronic Hepatitis B
Secondary ID [1] 0 0
2004-005120-41
Secondary ID [2] 0 0
GS-US-174-0103
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 - TDF
Treatment: Drugs - ADV
Treatment: Drugs - TDF placebo
Treatment: Drugs - ADV placebo
Treatment: Drugs - FTC/TDF

Experimental: TDF-TDF - TDF plus ADV placebo (double-blind period), followed by TDF (open-label period). Participants may add FTC (as part of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) FDC tablet) to their treatment regimen in the open-label period.

Active Comparator: ADV-TDF - ADV plus TDF placebo (double-blind period), followed by TDF (open-label period). Participants may add FTC (as part of FTC/TDF FDC tablet) to their treatment regimen in the open-label period.


Treatment: Drugs: TDF
300 mg tablet administered orally once daily

Treatment: Drugs: ADV
10 mg tablet administered orally once daily

Treatment: Drugs: TDF placebo
Tablet administered orally once daily

Treatment: Drugs: ADV placebo
Tablet administered orally once daily

Treatment: Drugs: FTC/TDF
200/300 mg fixed-dose combination (FDC) tablet administered orally 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 and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48
Timepoint [1] 0 0
Baseline; Week 48
Secondary outcome [1] 0 0
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96
Timepoint [2] 0 0
Week 96
Secondary outcome [3] 0 0
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384
Timepoint [3] 0 0
Weeks 144, 192, 240, 288, 336, and 384
Secondary outcome [4] 0 0
Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480
Timepoint [4] 0 0
Weeks 432 and 480
Secondary outcome [5] 0 0
Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Timepoint [5] 0 0
Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Secondary outcome [6] 0 0
Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Timepoint [6] 0 0
Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Secondary outcome [7] 0 0
Percentage of Participants With Histological Response at Week 48
Timepoint [7] 0 0
Baseline; Week 48
Secondary outcome [8] 0 0
Percentage of Participants With Histological Response at Week 240
Timepoint [8] 0 0
Baseline; Week 240
Secondary outcome [9] 0 0
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48
Timepoint [9] 0 0
Baseline; Week 48
Secondary outcome [10] 0 0
Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240
Timepoint [10] 0 0
Baseline; Week 240
Secondary outcome [11] 0 0
Ranked Assessment of Necroinflammation and Fibrosis at Week 48
Timepoint [11] 0 0
Baseline; Week 48
Secondary outcome [12] 0 0
Ranked Assessment of Necroinflammation and Fibrosis at Week 240
Timepoint [12] 0 0
Baseline; Week 240
Secondary outcome [13] 0 0
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48
Timepoint [13] 0 0
Baseline; Week 48
Secondary outcome [14] 0 0
Percentage of Participants With ALT Normalization at Week 96
Timepoint [14] 0 0
Baseline; Week 96
Secondary outcome [15] 0 0
Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384
Timepoint [15] 0 0
Baseline; Weeks 144, 192, 240, 288, 336, and 384
Secondary outcome [16] 0 0
Percentage of Participants With ALT Normalization at Weeks 432 and 480
Timepoint [16] 0 0
Baseline; Weeks 432 and 480
Secondary outcome [17] 0 0
Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Timepoint [17] 0 0
Baseline; Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480
Secondary outcome [18] 0 0
Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Timepoint [18] 0 0
Week 48; Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480
Secondary outcome [19] 0 0
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48
Timepoint [19] 0 0
Baseline; Week 48
Secondary outcome [20] 0 0
Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96
Timepoint [20] 0 0
Baseline; Week 96
Secondary outcome [21] 0 0
Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48
Timepoint [21] 0 0
Baseline; Week 48
Secondary outcome [22] 0 0
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96
Timepoint [22] 0 0
Baseline; Week 96
Secondary outcome [23] 0 0
Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480
Timepoint [23] 0 0
Baseline; Weeks 144, 192, 240, 288, 336, 384, 432, and 480
Secondary outcome [24] 0 0
Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance)
Timepoint [24] 0 0
Baseline; Week 48
Secondary outcome [25] 0 0
Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance)
Timepoint [25] 0 0
Baseline; Weeks 49 to 96
Secondary outcome [26] 0 0
Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance)
Timepoint [26] 0 0
Baseline; Weeks 97 to 144
Secondary outcome [27] 0 0
Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance)
Timepoint [27] 0 0
Baseline; Weeks 145 to 192
Secondary outcome [28] 0 0
Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance)
Timepoint [28] 0 0
Baseline; Weeks 193 to 240
Secondary outcome [29] 0 0
Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance)
Timepoint [29] 0 0
Baseline; Weeks 241 to 288
Secondary outcome [30] 0 0
Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance)
Timepoint [30] 0 0
Baseline; Weeks 289 to 336
Secondary outcome [31] 0 0
Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance)
Timepoint [31] 0 0
Baseline; Weeks 337 to 384
Secondary outcome [32] 0 0
Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance)
Timepoint [32] 0 0
Baseline; Weeks 385 to 432
Secondary outcome [33] 0 0
Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance)
Timepoint [33] 0 0
Baseline; Weeks 433 to 480

Eligibility
Key inclusion criteria
Key

A patient must meet all of the following inclusion criteria to be eligible for
participation in this study:

- Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B
s-antigen (HBsAg) for more than 6 months

- 18 through 69 years of age, inclusive

- Active hepatitis B e-antigen (HBeAg) positive chronic HBV infection, with all of the
following:

- HBeAg positive at screening

- Alanine aminotransferase (ALT) levels > 2 × ULN and = 10 × the upper limit of the
normal range (ULN)

- Serum HBV DNA > 1 million copies/mL at screening

- creatinine clearance = 70 mL/min

- hemoglobin = 8 g/dL

- neutrophils = 1,000 /mL

- Knodell necroinflammatory score = 3 and a Knodell fibrosis score < 4; however, up to
96 patients with cirrhosis, ie, a Knodell fibrosis score equal to 4, will be eligible
for enrollment

- Negative serum ß-human chorionic gonadotropin (hCG)

- Nucleotide naïve, ie, no prior nucleotide (TDF or ADV) therapy for > 12 weeks

- Nucleoside naïve, ie, no prior nucleoside (any nucleoside) therapy for > 12 weeks

- Willing and able to provide written informed consent

- Liver biopsy performed within 6 months of baseline and has readable biopsy slides or
agrees to have a biopsy performed prior to baseline

Key
Minimum age
18 Years
Maximum age
69 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
A patient who meets any of the following exclusion criteria is not to be enrolled in this
study:

- 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 unwilling to use an effective
method of contraception during the study; for males, condoms should be used and for
females, a barrier contraception method should be used

- Decompensated liver disease defined as conjugated bilirubin > 1.5 x ULN, prothrombin
time (PT) > 1.5 x ULN, platelets < 75,000/mL, serum albumin < 3.0 g/dL, or prior
history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy,
variceal hemorrhage)

- Received any nucleoside, nucleotide (TDF or ADV) or interferon (pegylated or not)
therapy within 6 months prior to the pre-treatment biopsy

- Evidence of hepatocellular carcinoma (HCC), ie, a-fetoprotein >50 ng/mL

- Coinfection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or
hepatitis delta virus (HDV)

- Significant renal, cardiovascular, pulmonary, or neurological disease

- Received solid organ or bone marrow transplantation

- Is currently receiving therapy with immunomodulators (eg, corticosteroids, etc.),
investigational agents, nephrotoxic agents, or agents susceptible of modifying renal
excretion

- Has proximal tubulopathy

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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 3
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
1/06/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2016
Sample size
Target
Accrual to date
Final
266
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- Concord
Recruitment hospital [3] 0 0
- Westmead
Recruitment hospital [4] 0 0
- Woolloongabba
Recruitment hospital [5] 0 0
- Clayton
Recruitment hospital [6] 0 0
- Footscray
Recruitment hospital [7] 0 0
- Parkville
Recruitment hospital [8] 0 0
- Prahran
Recruitment hospital [9] 0 0
- Fitzroy
Recruitment hospital [10] 0 0
- Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3011 - Footscray
Recruitment postcode(s) [7] 0 0
3050 - Parkville
Recruitment postcode(s) [8] 0 0
3004 - Prahran
Recruitment postcode(s) [9] 0 0
3065 - Fitzroy
Recruitment postcode(s) [10] 0 0
6000 - Perth
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
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Hawaii
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Bulgaria
State/province [11] 0 0
Sofia
Country [12] 0 0
Bulgaria
State/province [12] 0 0
Varna
Country [13] 0 0
Canada
State/province [13] 0 0
Alberta
Country [14] 0 0
Canada
State/province [14] 0 0
British Columbia
Country [15] 0 0
Canada
State/province [15] 0 0
Manitoba
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Czech Republic
State/province [17] 0 0
Brno
Country [18] 0 0
Czech Republic
State/province [18] 0 0
Hradec Kralove
Country [19] 0 0
Czech Republic
State/province [19] 0 0
Prague
Country [20] 0 0
Czech Republic
State/province [20] 0 0
Praha 6- Stresovice
Country [21] 0 0
France
State/province [21] 0 0
Clichy
Country [22] 0 0
France
State/province [22] 0 0
Grenoble
Country [23] 0 0
France
State/province [23] 0 0
Lille
Country [24] 0 0
France
State/province [24] 0 0
Lyon
Country [25] 0 0
France
State/province [25] 0 0
Nancy
Country [26] 0 0
France
State/province [26] 0 0
Paris
Country [27] 0 0
France
State/province [27] 0 0
Strasbourg
Country [28] 0 0
Germany
State/province [28] 0 0
Berlin
Country [29] 0 0
Germany
State/province [29] 0 0
Duesseldorf
Country [30] 0 0
Germany
State/province [30] 0 0
Dusseldorf
Country [31] 0 0
Germany
State/province [31] 0 0
Essen
Country [32] 0 0
Germany
State/province [32] 0 0
Hamburg
Country [33] 0 0
Germany
State/province [33] 0 0
Hannover
Country [34] 0 0
Germany
State/province [34] 0 0
Herne
Country [35] 0 0
Germany
State/province [35] 0 0
Homburg/Saar
Country [36] 0 0
Germany
State/province [36] 0 0
Kiel
Country [37] 0 0
Germany
State/province [37] 0 0
Mainz
Country [38] 0 0
Germany
State/province [38] 0 0
Munchen
Country [39] 0 0
Germany
State/province [39] 0 0
Tubingen
Country [40] 0 0
Greece
State/province [40] 0 0
Athens
Country [41] 0 0
Greece
State/province [41] 0 0
Thessaloniki
Country [42] 0 0
Italy
State/province [42] 0 0
Bologna
Country [43] 0 0
Netherlands
State/province [43] 0 0
Rotterdam
Country [44] 0 0
New Zealand
State/province [44] 0 0
Auckland
Country [45] 0 0
New Zealand
State/province [45] 0 0
Hamilton
Country [46] 0 0
New Zealand
State/province [46] 0 0
Wellington
Country [47] 0 0
New Zealand
State/province [47] 0 0
Whakatane
Country [48] 0 0
Poland
State/province [48] 0 0
Bialystok
Country [49] 0 0
Poland
State/province [49] 0 0
Bydgoszcz
Country [50] 0 0
Poland
State/province [50] 0 0
Chorzow
Country [51] 0 0
Poland
State/province [51] 0 0
Kielce
Country [52] 0 0
Poland
State/province [52] 0 0
Krakow
Country [53] 0 0
Poland
State/province [53] 0 0
Warszawa
Country [54] 0 0
Poland
State/province [54] 0 0
Wroclaw
Country [55] 0 0
Spain
State/province [55] 0 0
Barcelona
Country [56] 0 0
Spain
State/province [56] 0 0
Valencia
Country [57] 0 0
Turkey
State/province [57] 0 0
Ankara
Country [58] 0 0
Turkey
State/province [58] 0 0
Bursa
Country [59] 0 0
Turkey
State/province [59] 0 0
Istanbul
Country [60] 0 0
Turkey
State/province [60] 0 0
Izmir
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Birmingham
Country [62] 0 0
United Kingdom
State/province [62] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives of this study are to compare the efficacy, safety, and tolerability of
tenofovir disoproxil fumarate (TDF) versus adefovir dipivoxil (ADV) for the treatment of
HBeAg-positive chronic hepatitis B. Participants will receive TDF or ADV for 48 weeks
(double-blind). After 48 weeks, eligible participants switched to open-label TDF for up to
480 weeks.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00116805
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
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