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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00410072




Registration number
NCT00410072
Ethics application status
Date submitted
11/12/2006
Date registered
12/12/2006
Date last updated
15/03/2013

Titles & IDs
Public title
Entecavir Plus Tenofovir Combination Therapy Versus Entecavir Monotherapy in Naive Subjects With Chronic Hepatitis B
Scientific title
A Comparative Study of Chronic Hepatitis B Subjects Treated With Entecavir Plus Tenofovir Combination Therapy vs. Entecavir Monotherapy in Adults Who Are Treatment-Naive to Nucleosides and Nucleotides: The BE-LOW Study
Secondary ID [1] 0 0
AI463-110
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B, Chronic 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 - Entecavir
Treatment: Drugs - Entecavir + Tenofovir

Experimental: TDF 0.5 mg - TDF=tenofovir

Experimental: ETV 0.5 mg +TDF 300 mg - ETV=entecavir; TDF=tenofovir


Treatment: Drugs: Entecavir
Tablets, Oral, ETV = 0.5 mg, once daily, 100 weeks

Treatment: Drugs: Entecavir + Tenofovir
Tablets, Oral, ETV = 0.5 mg + TFV = 300 mg, once daily, 100 weeks

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

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Achieved Hepatitis B Virus DNA (HBV DNA) Levels <50 IU/mL by Polymerase Chain Reaction (PCR) at Week 96 - HBV DNA levels <50 IU/mL=approximately 300 copies/mL. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Timepoint [1] 0 0
At Week 96
Secondary outcome [1] 0 0
Percentage of Participants Who Achieved HBV DNA Levels <50 IU/mL by PCR at Week 48 and Week 96 by Hepatitis B e Antigen (HBeAg) Status - HBV DNA levels <50 IU/mL=approximately 300 copies/mL. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Timepoint [1] 0 0
At Weeks 48 and 96
Secondary outcome [2] 0 0
Percentage of Participants Who Achieved HBV DNA Levels <LOQ by PCR at Weeks 48 and 96 - LOQ=lower limit of quantitation. LOQ=29 IU/mL, or approximately 169 copies/mL. LOQ is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Limits of quantitation are matrix-, method-, and analyte-specific.Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Timepoint [2] 0 0
At Weeks 48 and 96
Secondary outcome [3] 0 0
Percentage of Participants Who Achieved HBV DNA Levels <LOD by PCR at Weeks 48 and 96 - LOD=Lower limit of detection. LOD) LOD=10 IU/mL, or approximately 58 copies/mL. LOD is the lowest concentration level that can be determined to be statistically different from a blank (99% confidence). The LOD is typically determined to be in the region where the signal to noise ratio is greater than 5. Limits of detection are matrix-, method-, and analyte-specific.Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Timepoint [3] 0 0
At Weeks 48 and 96
Secondary outcome [4] 0 0
Mean Log 10 HBV DNA at Weeks 48 and 96 - HBV DNA was analyzed by PCR, using the Roche COBAS®TaqMan - HPS assay. Reduction in Log 10 HBV count=reduced viral load.
Timepoint [4] 0 0
Baseline, Weeks 48 and 96
Secondary outcome [5] 0 0
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48 and 96 - ALT normalization= =1*upper limit of normal (ULN). Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Timepoint [5] 0 0
At Weeks 48 and 96
Secondary outcome [6] 0 0
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48 and 96 - HBeAg is a hepatitis B viral protein and is an indicator of active viral replication. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Timepoint [6] 0 0
At Weeks 48 and 96
Secondary outcome [7] 0 0
Percentage of Participants With HBeAg Seroconversion [( at Weeks 48 and 96 - HBeAg seroconversion=HBeAg loss and presence of hepatitis B e antibody (HBeAb). HBeAg is a hepatitis B viral protein and is an indicator of active viral replication.
Timepoint [7] 0 0
At Weeks 48 and 96
Secondary outcome [8] 0 0
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48 and 96 - HBsAg = A part of the hepatitis B virus. When found in the blood, HBsAg is an early marker of infection. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Timepoint [8] 0 0
At Weeks 48 and 96
Secondary outcome [9] 0 0
Percentage of Participants With HBsAg Seroconversion at Weeks 48 and 96 - HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection.
Timepoint [9] 0 0
At Weeks 48 and 96
Secondary outcome [10] 0 0
Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96 - Using the Roche COBAS TaqMan - HPS assay. Lower limit of Quantitation (LOQ) is the level above which quantitative results may be obtained with a specified degree of confidence. The LOQ is mathematically defined as equal to 10 times the standard deviation of the results for a series of replicates used to determine a justifiable limit of detection. Limits of quantitation are matrix-, method-, and analyte-specific.
Timepoint [10] 0 0
At Weeks 48 and 96
Secondary outcome [11] 0 0
Number of Participants With Adverse Events, Serious Adverse Events, and Discontinuations From Study Drug Due to Adverse Events or Laboratory Abnormalities - AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded.
Timepoint [11] 0 0
From enrollment through Week 100 + 24-week follow-up
Secondary outcome [12] 0 0
Number of Participants With HBV Resistance Through Week 48 - ETVr=entecavir resistance; TDFr=tenofovir resistance. HBV polymerase using the Trugene® HBV Genotyping Kit. HBV resistance: genotyping of HBV polymerase will be performed on stored viral samples at any timepoint when considered appropriate based on virologic response, including any specimen with detectable HBV DNA. When appropriate, phenotyping will also be used.
Timepoint [12] 0 0
Week 48
Secondary outcome [13] 0 0
Number of Participants With HBV Resistance at Week 96 - ETVr=entecavir resistance; TFDr=tenofovir resistance. HBV polymerase using the Trugene® HBV Genotyping Kit. HBV resistance: genotyping of HBV polymerase will be performed on stored viral samples at any timepoint when considered appropriate based on virologic response, including any specimen with detectable HBV DNA. When appropriate, phenotyping will also be used.
Timepoint [13] 0 0
Week 96
Secondary outcome [14] 0 0
Number of Participants With Virologic Breakthrough at Week 48 - ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough= confirmed >= 1 log10 increase in HBV DNA from the on-treatment nadir
Timepoint [14] 0 0
Week 48
Secondary outcome [15] 0 0
Number of Participants With Virologic Breakthrough at Week 96 - ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough=confirmed >=1 log10 increase in HBV DNA from moving nadir
Timepoint [15] 0 0
Week 96

Eligibility
Key inclusion criteria
- Chronic hepatitis B virus (HBV) infection (hepatitis B e antigen [HbeAg]-positive or
negative) disease

- Nucleoside- and nucleotide-naive

- Males or females =16 years of age (or minimum age of consent in a given country)

- Compensated liver function

- HBV DNA >1.72*10*5*IU/mL (approximately 10*6*copies/mL) for HbeAg-positive
participants

- HBV DNA >1.72*10*4*IU/mL (approximately 10*5*copies/mL) for Hbe-Ag-negative
participants

- Alanine aminotransferase level =*upper limit of normal (ULN) and =10*ULN
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Evidence of decompensated cirrhosis

- Coinfection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus

- Laboratory values out of protocol-specified range

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
Open (masking not used)
Who is / are masked / blinded?



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
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
Local Institution - Westmead Nsw
Recruitment hospital [2] 0 0
Local Institution - Clayton Vic
Recruitment hospital [3] 0 0
Local Institution - Fitzroy
Recruitment hospital [4] 0 0
Local Institution - Heidelberg
Recruitment hospital [5] 0 0
Local Institution - Prahan
Recruitment postcode(s) [1] 0 0
2145 - Westmead Nsw
Recruitment postcode(s) [2] 0 0
3168 - Clayton Vic
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3004 - Prahan
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
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
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
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Argentina
State/province [10] 0 0
Prov De Santa
Country [11] 0 0
Brazil
State/province [11] 0 0
Minas Gerais
Country [12] 0 0
Brazil
State/province [12] 0 0
Rio Grande Do Sul
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
France
State/province [17] 0 0
Grenoble Cedex 09
Country [18] 0 0
France
State/province [18] 0 0
Marseille Cedex 08
Country [19] 0 0
France
State/province [19] 0 0
Paris Cedex 12
Country [20] 0 0
France
State/province [20] 0 0
Paris Cedex 13
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
France
State/province [22] 0 0
Strasbourg
Country [23] 0 0
India
State/province [23] 0 0
Andhra Pradesh
Country [24] 0 0
India
State/province [24] 0 0
Lucknow
Country [25] 0 0
India
State/province [25] 0 0
Ludhiana
Country [26] 0 0
India
State/province [26] 0 0
Vellore
Country [27] 0 0
Italy
State/province [27] 0 0
Antella Firenze
Country [28] 0 0
Italy
State/province [28] 0 0
Brescia
Country [29] 0 0
Italy
State/province [29] 0 0
Pisa
Country [30] 0 0
Italy
State/province [30] 0 0
Roma
Country [31] 0 0
Mexico
State/province [31] 0 0
Durango
Country [32] 0 0
Poland
State/province [32] 0 0
Bialystok
Country [33] 0 0
Poland
State/province [33] 0 0
Chorzow
Country [34] 0 0
Poland
State/province [34] 0 0
Krakow
Country [35] 0 0
Poland
State/province [35] 0 0
Lublin
Country [36] 0 0
Poland
State/province [36] 0 0
Warszawa
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Moscow
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Smolensk
Country [39] 0 0
Russian Federation
State/province [39] 0 0
St. Petersburg
Country [40] 0 0
South Africa
State/province [40] 0 0
Gauteng
Country [41] 0 0
South Africa
State/province [41] 0 0
Western Cape
Country [42] 0 0
Turkey
State/province [42] 0 0
Bornova Izmir
Country [43] 0 0
Turkey
State/province [43] 0 0
Cebeci Ankara
Country [44] 0 0
Turkey
State/province [44] 0 0
Sihhiye Ankara
Country [45] 0 0
Turkey
State/province [45] 0 0
Trabzon

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to compare the effectiveness of entecavir plus tenofovir
combination therapy with that of entecavir monotherapy. Safety will also be studied.
Trial website
https://clinicaltrials.gov/show/NCT00410072
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
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