Clinical Trial: Phase 3 Study of GSK548470 in Patients With Compensated Chronic Hepatitis B With Poor Response to Other Drugs

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

Official Title: A Multi-center, Open-label Study of GSK548470 (Tenofovir Disoproxil Fumarate) in Patients With Compensated Chronic Hepatitis B With Poor Response to Other Drugs

Brief Summary: The purpose of this study is to evaluate the efficacy and safety of once-daily treatment with GSK548470 300 mg in Japanese patients with compensated chronic hepatitis B with poor response to other drugs.

Detailed Summary: This is a multicenter, open-label study in Japanese patients with compensated chronic hepatitis B with poor response to other drugs in order to evaluate the efficacy and safety of GSK548470 administered at a dose of 300 mg once daily. The target sample size is set at 32 subjects. The primary objective is to evaluate the efficacy and safety of once-daily treatment with GSK548470 300 mg in subjects with compensated chronic hepatitis B with poor response to other drugs. The secondary objective is to evaluate the long-term efficacy and safety of once-daily treatment with GSK548470 300 mg.To evaluate the efficacy and safety of GSK548470 in the study, subjects receiving a combination of lamivudine (LAM) and adefovir pivoxil (ADV) will be switched to a combination of LAM and GSK548470, while subjects on entecavir hydrate (ETV) with or without ADV will be switched to a combination of ETV and GSK548470.
Sponsor: GlaxoSmithKline

Current Primary Outcome: Number of Participants With HBV DNA Level < 2.1 log10 Copies/mL at Week 24 [ Time Frame: Week 24 ]

The number of participants with serum hepatitis B virus deoxyribonucleic acid (HBV DNA) level < the lower limit of quantitation (2.1 log10 copies/millilitres[copies/mL]) (i.e., the rate of suppression) at Week 24 was summarized. Statistical analysis was not provided for the number of participants achieving HBV DNA <2.1 log10 copies/mL (at Week 24). Missing values observed during the treatment period was imputed by the last observation carried forward (LOCF) method.


Original Primary Outcome: Proportion of subjects with serum HBV DNA < 2.1 log10 copies/mL at week 24 [ Time Frame: Week 24 ]

Current Secondary Outcome:

  • Mean Change From Baseline in Serum HBV DNA Level at Week 24, Week 48 and Week 96 [ Time Frame: Baseline and Week 24, Week 48 and Week 96 ]
    The mean change from Baseline in the hepatitis B virus deoxyribonucleic acid (HBV DNA) level at Week 24, Week 48 and Week 96 were assessed (HBV DNA values below the lower limit of quantitation [i.e. 2.1 log10 copies/mL] for the assay were set to the lower limit minus 0.1 [i.e. 2.0 log10 copies/mL]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Last Observation Carried Forward (LOCF) method was applied for missing values.
  • Number of Participants With Serum HBV DNA < 2.1 log10 Copies/mL at Week 48 and Week 96 [ Time Frame: Week 48 and Week 96 ]
    The number of participants with serum HBV DNA level < the lower limit of quantitation (2.1 log10 copies/mL) (i.e., the rate of suppression) at 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 hepatitis Be antigen (HBeAg)/hepatitis B e 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 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 hepatitis B surface antigen (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 was defined as change of detectable antibody to HBsAg from negative to positive. The LOCF method was applied for missing values.
  • Number of Participants With Virological Breakthrough and Resistance-related Mutations [ Time Frame: Screening, Week 24, Week 48, Week 96 and Virological Breakthrough ]
    The number of participants who harbored resistance-related mutations and developed virological breakthrough was summarized. Virological breakthrough defined as HBV DNA level increase >=1 log10 copies/mL above the treatment nadir were analyzed through end of treatment. Subjects who achieved the HBV-DNA values below lower limit of quantification (LLQ) (< 2.1 log10 copies/mL) in quantitative analysis at Week 96 were also considered "negative" in drug-resistance without implementation of genotypic analysis. Lamivudine (LAM), adefovir pivoxil (ADV), and entecavir hydrate (ETV) resistance-related mutations were analyzed at Screening (i.e. Baseline), Week 24, Week 48 and Week 96 in participants with HBV DNA level above the lower limit of detection. Virologic breakthrough was defined as 1.0 log10 or greater increases in serum HBV DNA levels from on-treatment nadir. 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 hepatitis B surface antigen (HBsAg) category (HBsAg <80, 80 to 800, 800 to 8000, 8000 to 80000, >=80000) (kilo international unit per liter [KIU/L]) by study visit was summarized.
  • 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 ]

    Original Secondary Outcome:

    • Mean change of serum HBV DNA from baseline at week 24, 48, 96 [ Time Frame: Week 24, 48, 96 ]
    • Proportion of subjects with serum HBV DNA < 2.1 log10 copies/mL at week 48, 96 [ Time Frame: Week 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/or 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 17, 2011
    Date Started: December 2011
    Date Completion:
    Last Updated: June 18, 2015
    Last Verified: May 2015