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Completed

NCT Number: NCT00410072

Entecavir Plus Tenofovir Combination Therapy Versus Entecavir Monotherapy in Naive Subjects With Chronic Hepatitis B

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.

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Key information

Conditions

Hepatitis B, Chronic Blood-Borne Infections Chronic Disease Communicable Diseases DNA Virus Infections Digestive System Diseases Disease Attributes Hepadnaviridae Infections Hepatitis Hepatitis B Hepatitis, Chronic Hepatitis, Viral, Human Infections Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Virus Diseases

Age range

16 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Local Institution, Ciudad de Buenos Aires, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Entecavir

Drug

Tablets, Oral, ETV = 0.5 mg, once daily, 100 weeks

Other names: Baraclude, BMS-200475

Entecavir + Tenofovir

Drug

Tablets, Oral, ETV = 0.5 mg + TFV = 300 mg, once daily, 100 weeks

Other names: Baraclude, BMS-200475

Primary outcomes

  1. Percentage of Participants Who Achieved Hepatitis B Virus DNA (HBV DNA) Levels <50 IU/mL by Polymerase Chain Reaction (PCR) at Week 96

    Time frame: 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.

Secondary outcomes

  1. 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

    Time frame: At Weeks 48 and 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.

  2. Percentage of Participants Who Achieved HBV DNA Levels <LOQ by PCR at Weeks 48 and 96

    Time frame: 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.

  3. Percentage of Participants Who Achieved HBV DNA Levels <LOD by PCR at Weeks 48 and 96

    Time frame: 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.

  4. Mean Log 10 HBV DNA at Weeks 48 and 96

    Time frame: Baseline, 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.

  5. Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48 and 96

    Time frame: 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.

  6. Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48 and 96

    Time frame: 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.

  7. Percentage of Participants With HBeAg Seroconversion [( at Weeks 48 and 96

    Time frame: 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.

  8. Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48 and 96

    Time frame: 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.

  9. Percentage of Participants With HBsAg Seroconversion at Weeks 48 and 96

    Time frame: At Weeks 48 and 96

    HBsAg = a part of the hepatitis B virus that, when in the blood, is an early marker of infection.

  10. Number of Participants With HBV DNA in Relevant Categories at Weeks 48 and 96

    Time frame: 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.

  11. Number of Participants With Adverse Events, Serious Adverse Events, and Discontinuations From Study Drug Due to Adverse Events or Laboratory Abnormalities

    Time frame: From enrollment through Week 100 + 24-week follow-up

    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.

  12. Number of Participants With HBV Resistance Through Week 48

    Time frame: 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.

  13. Number of Participants With HBV Resistance at Week 96

    Time frame: 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.

  14. Number of Participants With Virologic Breakthrough at Week 48

    Time frame: Week 48

    ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough= confirmed >= 1 log10 increase in HBV DNA from the on-treatment nadir

  15. Number of Participants With Virologic Breakthrough at Week 96

    Time frame: Week 96

    ETVr=entecavir resistance; TFDr=tenofovir resistance. Virologic breakthrough=confirmed >=1 log10 increase in HBV DNA from moving nadir

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study 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

Important dates

Study start
2007
Primary completion
2010
Study completion
2010
First posted
Dec 12, 2006
Registry last updated
Mar 15, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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