Clinical Trial: Phase 3 Study of GSK548470 in Patients With Compensated Chronic Hepatitis B Untreated With Nucleic Acid Analogue

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multi-center, Randomized, Active Controlled, Double-blind, Parallel Group Comparison Study and Subsequent Open-label Study of GSK548470 in Patients With Compensated Chronic Hep

Brief Summary: The purpose of this study is to evaluate the efficacy and safety of GSK548470 administered once daily at a dose level of 300 mg to Japanese patients with compensated chronic hepatitis B untreated with any nucleic acid analogue. In efficacy, the non-inferiority of GSK548470 to ETV will be verified using the antiviral effect as the index.

Detailed Summary: This study is a multicenter, randomized, active comparator-controlled, double-blind, parallel-group comparison study in Japanese patients with compensated chronic hepatitis B untreated with any nucleic acid analogue and its subsequent open-label study. Efficacy and safety will be compared between once-daily dosing of GSK548470 300 mg and once-daily dosing of ETV 0.5 mg, and subsequently the efficacy and safety of GSK548470 administered long term will be investigated. A total of 165 subjects will be assigned to the GSK548470 group or the ETV group at a ratio of 2:1. The subjects will be assigned by stratified randomization in terms of HBe antigen and serum HBV-DNA level. The primary purpose is to verify the non-inferiority of GSK548470 to ETV using as an index the change amount of HBV-DNA level at Week 24 from the baseline level. The secondary purpose is to investigate the efficacy and safety of GSK548470 300 mg administered once daily for a long term.
Sponsor: GlaxoSmithKline

Current Primary Outcome: Mean Change From Baseline in Serum HBV DNA Level at Week 24 [ Time Frame: Baseline and Week 24 ]

The mean change from Baseline in the hepatitis B virus deoxyribonucleic acid (HBV DNA) level at Week 24 was assessed (lower limit of quantitation : 2.1 log 10 copies/mL). The mean values were adjusted by Baseline HBV DNA levels. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.


Original Primary Outcome: Mean change of serum HBV-DNA from baseline at week 24 [ Time Frame: Week 24 ]

Current Secondary Outcome:

  • Mean Change From Baseline in Serum HBV DNA Level at Week 48 and Week 96 [ Time Frame: Baseline, Week 48 and Week 96 ]
    The mean change from Baseline in the HBV DNA level at Week 48 and Week 96 were assessed (lower limit of quantitation : 2.1 log10 copies/mL). The mean values were adjusted by Baseline HBV DNA levels. Change from Baseline was calculated as the post-baseline value minus the Baseline value. The LOCF method was applied for missing values.
  • Number of Participants With Serum HBV DNA < 2.1 log10 Copies/mL at Week 24, Week 48 and Week 96 [ Time Frame: Week 24, Week 48 and Week 96 ]
    The number of participants with serum HBV DNA level less than the lower limit of quantitation (i.e. 2.1 log10 copies/mL) at Week 24, Week 48 and Week 96 were summarized. The LOCF method was applied for missing values.
  • Number of Participants With Alanine Aminotransferase (ALT) Normalization at Week 24, Week 48 and Week 96 [ Time Frame: Week 24, Week 48 and Week 96 ]
    The number of participants with alanine aminotransferase (ALT) normalization at Week 24, Week 48 and Week 96 were summarized. ALT normalization is defined as when an ALT value exceeds the upper limit of normal range (ULN) at Baseline and within the normal range at the end of treatment. The LOCF method was applied for missing values.
  • Number of Participants With HBeAg Loss at Week 24, Week 48 and Week 96 [ Time Frame: Week 24, Week 48 and Week 96 ]
    The number of participants achieving hepatitis Be antigen (HBeAg) loss at Week 24, Week 48 and Week 96 in positive HBeAg participants at Baseline were summarized. Loss of HBeAg is defined as the change of detectable HBeAg from positive to negative. The LOCF method was applied for missing values.
  • Number of Participants With HBeAg/HBeAb Seroconversion at Week 24, Week 48 and Week 96 [ Time Frame: Week 24, Week 48 and Week 96 ]
    The number of participants achieving HBeAg/hepatitis Be antibody (HBeAb) seroconversion at Week 24, Week 48 and Week 96 in positive HBeAg and negative HBeAb participants at Baseline were summarized. Seroconversion to HBeAg is defined as the change of detectable antibody to HBeAg from negative to positive. The LOCF method was applied for missing values.
  • Number of Participants Achieving HBsAg Loss at Week 24, Week 48 and Week 96 [ Time Frame: Week 24, Week 48 and Week 96 ]
    The number of participants with hepatitis B surface antigen (HBsAg) loss at Week 24, Week 48 and Week 96 in positive HBsAg participants at Baseline were summarized. Loss of HBsAg is defined as change of detectable HBsAg from positive to negative. The LOCF method was applied for missing values.
  • Number of Participants Achieving HBsAg/HBsAb Seroconversion at Week 24, Week 48 and Week 96 [ Time Frame: Week 24, Week 48 and Week 96 ]
    The number of participants with HBsAg/hepatitis B surface antibody (HBsAb) seroconversion at Week 24, Week 48 and Week 96 in positive HBsAg and negative HBsAb participants at Baseline were summarized. HBsAg seroconversion .is defined as change of detectable antibody to HBsAg from negative to positive. The LOCF method was applied for missing values.
  • Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96 [ Time Frame: Baseline, Week 24, Week 48 and Week 96 ]
    The number of participants achieving each indicated HBsAg category (HBsAg <80, 80 to 800, 800 to 8000, 8000 to 80000, and >=80000) (kilo international unit per liter [KIU/L]) by study visit was summarized. The LOCF method was applied for missing values.
  • Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96 [ Time Frame: Baseline, Week 24, Week 48 and Week 96 ]
    The number of participants achieving each indicated hepatitis B core-related antigen (HBcrAg) category (HBcrAg <3.0, 3.0 to 4.0, 4.0 to 5.0, 5.0 to 6.0, and >=6.0) (Log kilo unit per liter [KU/L]) by study visit was summarized. The LOCF method was applied for missing values.
  • Number of Participants With Virological Breakthrough Through End of the Study [ Time Frame: From Baseline to throughout study ]
    The number of participants who experienced virological breakthrough was summarized. Virological breakthrough is defined as serum HBV DNA level increase >=1 log10 copies/mL above the treatment nadir. Virological breakthrough values were presented from Baseline to through out the study. Baseline is defined as the value at Week 0 visit.
  • Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study) [ Time Frame: Screening, Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to throughout the study) ]
    The development of drug resistance-related (RA) mutations was analyzed to look for resistance to Lamivudine (LAM), Adefo

    Original Secondary Outcome:

    • Mean change of serum HBV DNA from baseline at week 48, 96 [ Time Frame: Week 48, 96 ]
    • Proportion of subjects with serum HBV DNA < 2.1 log10 copies/mL at week 24, 48, 96 [ Time Frame: Week 24, 48, 96 ]
    • Proportion of subjects with ALT normalization at week 24, 48, 96 [ Time Frame: Week 24, 48, 96 ]
    • Proportion of subjects achieving HBeAg loss, HBeAg /Ab seroconversion at week 24, 48, 96 in HBeAg positive subjects [ Time Frame: Week 24, 48, 96 ]
    • Proportion of subjects achieving HBsAg loss and HBsAg/Ab seroconversion at week 24, 48, 96 [ Time Frame: Week 24, 48, 96 ]
    • Proportion of subjects with resistant mutation and virologic breakthrough (defined as HBV-DNA level increase >=1 log10 copies/mL above the treatment nadir) at week 24, 48, 96 [ Time Frame: Week 24, 48, 96 ]
    • Reduction in quantitative HBsAg at week 24, 48, 96 [ Time Frame: Week 24, 48, 96 ]
    • Reduction in quantitative HBcrAg at week 24, 48, 96 [ Time Frame: Week 24, 48, 96 ]


    Information By: GlaxoSmithKline

    Dates:
    Date Received: November 23, 2011
    Date Started: November 2011
    Date Completion:
    Last Updated: July 7, 2016
    Last Verified: July 2016