Hepatitis B, Chronic Clinical Trial
Official 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
Verified date | March 2013 |
Source | Bristol-Myers Squibb |
Contact | n/a |
Is FDA regulated | No |
Health authority | United States: Food and Drug Administration |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 669 |
Est. completion date | October 2010 |
Est. primary completion date | October 2010 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 16 Years and older |
Eligibility |
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 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 |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Argentina | Local Institution | Ciudad De Buenos Aires | Buenos Aires |
Argentina | Local Institution | Ciudad De Buenos Aires | Buenos Aires |
Argentina | Local Institution | Ciudad De Buenos Aires | Buenos Aires |
Argentina | Local Institution | Rosario | Prov De Santa |
Australia | Local Institution | Clayton Vic | Victoria |
Australia | Local Institution | Fitzroy | Victoria |
Australia | Local Institution | Heidelberg | Victoria |
Australia | Local Institution | Prahan | Victoria |
Australia | Local Institution | Westmead Nsw | New South Wales |
Brazil | Local Institution | Belo Horizonte | Minas Gerais |
Brazil | Local Institution | Porto Alegre Rs | Rio Grande Do Sul |
Canada | Local Institution | Calgary | Alberta |
Canada | Local Institution | Toronto | Ontario |
Canada | Local Institution | Toronto | Ontario |
Canada | Local Institution | Toronto | Ontario |
Canada | Local Institution | Vancouver | British Columbia |
Canada | Local Institution | Winnipeg | Manitoba |
France | Local Institution | Grenoble Cedex 09 | |
France | Local Institution | Marseille Cedex 08 | |
France | Local Institution | Paris | |
France | Local Institution | Paris Cedex 12 | |
France | Local Institution | Paris Cedex 13 | |
France | Local Institution | Strasbourg | |
India | Local Institution | Hyderabad | Andhra Pradesh |
India | Local Institution | Lucknow | |
India | Local Institution | Ludhiana | |
India | Local Institution | Vellore | |
Italy | Local Institution | Antella Firenze | |
Italy | Local Institution | Brescia | |
Italy | Local Institution | Pisa | |
Italy | Local Institution | Roma | |
Mexico | Local Institution | Durango | |
Poland | Local Institution | Bialystok | |
Poland | Local Institution | Chorzow | |
Poland | Local Institution | Krakow | |
Poland | Local Institution | Lublin | |
Poland | Local Institution | Warszawa | |
Russian Federation | Local Institution | Moscow | |
Russian Federation | Local Institution | Moscow | |
Russian Federation | Local Institution | Moscow | |
Russian Federation | Local Institution | Smolensk | |
Russian Federation | Local Institution | St. Petersburg | |
Russian Federation | Local Institution | St. Petersburg | |
Russian Federation | Local Institution | St. Petersburg | |
Russian Federation | Local Institution | St. Petersburg | |
South Africa | Local Institution | Bellville | Western Cape |
South Africa | Local Institution | N1 City Goodwood | Western Cape |
South Africa | Local Institution | Pretoria | Gauteng |
Turkey | Local Institution | Bornova Izmir | |
Turkey | Local Institution | Cebeci Ankara | |
Turkey | Local Institution | Sihhiye Ankara | |
Turkey | Local Institution | Trabzon | |
United States | University Of Michigan Health System | Ann Arbor | Michigan |
United States | Atlanta Gastroenterology Associates | Atlanta | Georgia |
United States | Digestive Healthcare Of Georgia | Atlanta | Georgia |
United States | Digestive Disease Associates, P.A. | Baltimore | Maryland |
United States | Beth Israel Deaconess Medical Center | Boston | Massachusetts |
United States | Sing Chan, Md | Flushing | New York |
United States | Maryland Digestive Disease Research, Llc | Laurel | Maryland |
United States | Sergio E. Rojter | Los Angeles | California |
United States | North Shore University | Manhasset | New York |
United States | University Of Miami | Miami | Florida |
United States | Yale University School Of Medicine | New Haven | Connecticut |
United States | Beth Israel Medical Center | New York | New York |
United States | Concorde Medical Group | New York | New York |
United States | Mount Sinai School Of Medicine | New York | New York |
United States | Tuan Nguyen, Md | San Diego | California |
United States | San Jose Gastroenterology | San Jose | California |
Lead Sponsor | Collaborator |
---|---|
Bristol-Myers Squibb |
United States, Argentina, Australia, Brazil, Canada, France, India, Italy, Mexico, Poland, Russian Federation, South Africa, Turkey,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | At Week 96 | No |
Secondary | 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. | At Weeks 48 and 96 | No |
Secondary | 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. | At Weeks 48 and 96 | No |
Secondary | 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. | At Weeks 48 and 96 | No |
Secondary | 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. | Baseline, Weeks 48 and 96 | No |
Secondary | 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. | At Weeks 48 and 96 | No |
Secondary | 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. | At Weeks 48 and 96 | No |
Secondary | 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. | At Weeks 48 and 96 | No |
Secondary | 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. | At Weeks 48 and 96 | No |
Secondary | 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. | At Weeks 48 and 96 | No |
Secondary | 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. | At Weeks 48 and 96 | No |
Secondary | 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. | From enrollment through Week 100 + 24-week follow-up | Yes |
Secondary | 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. | Week 48 | No |
Secondary | 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. | Week 96 | No |
Secondary | 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 | Week 48 | No |
Secondary | 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 | Week 96 | No |
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