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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Kitrinos KM, Corsa A, Liu Y, Flaherty J, Snow-Lamp... [More Details]
Journal Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, ... [More Details]
Journal Gordon SC, Krastev Z, Horban A, Petersen J, Sperl ... [More Details]
Journal Tsai NC, Marcellin P, Buti M, Washington MK, Lee S... [More Details]
Journal Fung S, Gordon SC, Krastev Z, Horban A, Petersen J... [More Details]
Journal Marcellin P, Buti M, Krastev Z, de Man RA, Zeuzem ... [More Details]
Journal Buti M, Fung S, Gane E, Afdhal NH, Flisiak R, Gure... [More Details]
Journal Buti M, Tsai N, Petersen J, Flisiak R, Gurel S, Kr... [More Details]
Journal Liu Y, Corsa AC, Buti M, Cathcart AL, Flaherty JF,... [More Details]
Journal Corsa A, Liu Y, Flaherty JF, Marcellin P, Miller M... [More Details]
Journal Marcellin P, Gane EJ, Flisiak R, Trinh HN, Peterse... [More Details]
Journal Gane EJ, Marcellin P, Sievert W, Trinh HN, Shiffma... [More Details]

Results are available at https://clinicaltrials.gov/study/NCT00116805