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Trial record 36 of 223 for:    "Hepatitis B" | "Tenofovir"

Efficacy and Safety Study of Entecavir Plus Tenofovir in Patients With Chronic Hepatitis B Who Failed Previous Treatment

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ClinicalTrials.gov Identifier: NCT01063036
Recruitment Status : Completed
First Posted : February 5, 2010
Results First Posted : February 13, 2014
Last Update Posted : December 15, 2014
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE February 3, 2010
First Posted Date  ICMJE February 5, 2010
Results First Submitted Date  ICMJE November 5, 2013
Results First Posted Date  ICMJE February 13, 2014
Last Update Posted Date December 15, 2014
Study Start Date  ICMJE May 2010
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 30, 2013)
Percentage of Participants With a Virologic Response at Week 48 - Treated Population [ Time Frame: Week 48 ]
Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL. Percentage was calculated as number of participants with virologic response at Week 48 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F). The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay, in a central laboratory. The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
Original Primary Outcome Measures  ICMJE
 (submitted: February 4, 2010)
Proportion of subjects who achieve a virological response defined as HBV DNA < 50 IU/mL at Week 48 [ Time Frame: Week 48 ]
Change History Complete list of historical versions of study NCT01063036 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 25, 2014)
  • Percentage of Participants With a Virologic Response at Week 24 and at Week 96 - Treated Population [ Time Frame: Week 24, Week 96 ]
    Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL. Percentage was calculated as number of participants with virologic response at Week 24, Week 96 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F). The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay. The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
  • Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population [ Time Frame: Baseline to Weeks 12, 24, 48, 96 ]
    HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay. The results were reported in log 10 IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ. Baseline was Day 1, prior to study drug administration.
  • Percentage of Participants With HBV DNA Less Than the Lower Limit of Detection (LLD) at Weeks 24, 48, and 96 - Treated Population [ Time Frame: Weeks 24, 48, 96 ]
    HBV DNA less than (<) LLD (6 IU/mL) was defined/measured by the COBAS(REGISTERED) TaqMan HPS assay at Weeks 24, 48, and 96. Percentage was calculated as number of participants with HBV DNA < LLD at Weeks 24, 48, 96 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F).
  • Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg Positive at Baseline [ Time Frame: Baseline to Weeks 24, 48, and 96 ]
    Loss of HBeAg was defined as being HBeAg-negative at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline. Method used for HBeAg was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples. Percentage was calculated as number of participants with HBeAg loss at Weeks 24 and 48 divided by the number of treated participants who were HBeAg-positive at baseline. Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug.
  • Percentage of Participants With HBe Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg-positive at Baseline [ Time Frame: Baseline, Weeks 24, 48, and 96 ]
    HBe seroconversion was defined as being both HBeAg-negative and HBeAb-positive at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline. Method used was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples. Percentage was calculated as number of participants with HBe seroconversion at Weeks 24, 48, and 96 divided by the number of treated participants who were HBeAg-positive at baseline. Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug.
  • Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 24, 48, 96 - Treated Population Who Were HBsAg-Positive at Baseline [ Time Frame: Baseline, Weeks 24, 48, 96 ]
    Loss of HBsAg was defined as being HBsAg-negative at Weeks 24, 48, 96 in those participants who had been HBsAg-positive at baseline. The method used: Immunoassay - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma (potassium ethylene diamine tetraacetic acid, lithium or sodium heparinized). Percentage calculated as number of participants with a HBsAg loss at Weeks 24, 48, and 96 divided by the number of treated participants who were HBsAg-positive at baseline (participants were not enrolled into the study unless they were positive for HBsAg). Treated participants (HBsAg-positive at baseline) were evaluated using NC=F. Baseline was Day 1, before start of study drug.
  • Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBsAg-Positive at Baseline [ Time Frame: Baseline, Weeks 24, 48, and 96 ]
    HBsAg seroconversion was defined as being both HBsAg-negative and HBsAb-positive at Weeks 24, 48, and 96 in those participants who had been HBsAg-positive at baseline. Percentage was calculated as number of participants with HBs seroconversion at Weeks 24 and 48 divided by the number of treated participants who were HBsAg-positive at baseline. Positive result for HBsAg was one of the inclusion criteria. Treated participants (HBsAg positive at baseline) were evaluated using NC=F. The method used was an Immunoassay testing - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma [potassium ethylenediaminetetraacetic acid (EDTA), lithium or sodium heparinized]. Baseline was Day 1, before start of study drug.
  • Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) on Treatment, and Discontinuation of Study Drug Due to Adverse Events (AE) - Treated Population [ Time Frame: Day 1 to last dose of study drug plus 5 days; up to Week 96 ]
    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. On-treatment = on Day 1 through last dose of study therapy + 5 days.
  • Number of Participants With Emergence of Genotypic Resistance to Study Drugs at Weeks 48 and 96- Treated Population [ Time Frame: Baseline to Weeks 48, 96 ]
    Testing of HBV genotype was performed at baseline for all treated patients and for participants at Weeks 48 and 96 with primary non-response or virologic breakthrough. Emergent genotypic resistance to study drugs was defined as follows: Emergent = not detected at baseline; entecavir (ETV) resistance (ETVr): participant's sample was to have rtM204V/I/S and any substitution at rtT184, rtS202, or rtM250; tenofovir (TDF) resistance (TDFr) which was based on adefovir (ADV)-mutations: participant's sample was to have rtA181T/V, rtN236T, or (rtA194T and rtM204V/I/S). Primary non-response was defined as < 1 log10 decrease in HBV DNA from baseline on treatment at or after Week 12. Virologic breakthrough was defined as ≥ 1 log10 increase in HBV DNA over nadir on treatment, either confirmed or last on-treatment followed by discontinuation of study therapy.
  • Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population [ Time Frame: Day 1 to last dose of study drug plus 5 days; up to Week 96 ]
    Selected criteria presented in each category. Upper limit of normal among all laboratory ranges (ULN); Baseline (BL); alanine transaminase (ALT); milligram per deciliter (mg/dL); milliliters per minute (mL/min); greater than (>);greater than, equal to (>=); less than (<). Creatinine data presented below were confirmed, ie, at least 2 consecutive values. On-treatment = after Day 1 through last dose of study therapy + 5 days.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2010)
  • Proportion of subjects with undetectable HBV DNA (< 50 IU/mL) [ Time Frame: Weeks 24 and 96 ]
  • Proportion of subjects who achieve HBV DNA < the lower limit of detection (LLD) [ Time Frame: Weeks 24, 48 and 96 ]
  • To evaluate changes in HBeAg and HBsAg status [ Time Frame: Weeks 24, 48 and 96 ]
  • To evaluate the emergence of resistant mutations during treatment with entecavir plus tenofovir [ Time Frame: Day 1, Week 12, 24, 36, 48, 72, 96 (or End of Treatment) ]
  • To evaluate mean change of viral load from baseline [ Time Frame: Week 12 ]
  • To assess the long-term safety of the combination therapy of entecavir plus tenofovir. This will be done through the collection of Adverse Events, Serious Adverse Events, and discontinuations from study drug due to adverse events. [ Time Frame: All: Day 1, Weeks 12, 24, 36, 48, 72, 96 (or End of Treatment). Only SAEs and Hepatitis B related diagnoses at Weeks 6 and 24 post-dosing. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety Study of Entecavir Plus Tenofovir in Patients With Chronic Hepatitis B Who Failed Previous Treatment
Official Title  ICMJE A Study of the Safety and Efficacy of Entecavir Plus Tenofovir in Adults With Chronic Hepatitis B Virus Infection With Previous Nucleoside/Nucleotide Treatment Failure
Brief Summary The purpose of this study is to show that the combination of entecavir and tenofovir, is effective and well tolerated in chronic hepatitis B patients who have failed previous treatment.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Hepatitis B
Intervention  ICMJE
  • Drug: Entecavir
    Tablets, Oral, 1 mg, once daily, 96 weeks
    Other Names:
    • Baraclude®
    • BMS-200475
  • Drug: Tenofovir
    Tablets, Oral, 300 mg, once daily, 96 weeks
    Other Name: Viread®
Study Arms  ICMJE Experimental: Entecavir + Tenofovir
Interventions:
  • Drug: Entecavir
  • Drug: Tenofovir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 30, 2013)
144
Original Estimated Enrollment  ICMJE
 (submitted: February 4, 2010)
100
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects with chronic hepatitis B virus (HBV) infection; either hepatitis B-e antigen(HBeAg)-negative or HBeAg-positive
  • Subjects must have a treatment failure to their current nucleoside/ nucleotide treatment regimen
  • Prior entecavir and/or tenofovir monotherapy is allowed
  • Subjects must have compensated liver function

Exclusion Criteria:

  • Women who are pregnant or breastfeeding
  • Evidence of decompensated cirrhosis
  • Co-infection with HIV, hepatitis C virus (HCV), or hepatitis D virus (HDV)
  • Moderate or severe renal impairment
  • Recent history of pancreatitis
  • Therapy with interferon, thymosin alpha or other immuno-stimulators within 24 weeks of being assigned to study drug into this study
  • Prior entecavir/tenofovir combination therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   Italy,   Netherlands,   Poland,   Romania,   Spain
Removed Location Countries Portugal
 
Administrative Information
NCT Number  ICMJE NCT01063036
Other Study ID Numbers  ICMJE AI463-203
2009-015705-40 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP