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

July 7, 2016 updated by: GlaxoSmithKline

A Multi-center, Randomized, Active Controlled, Double-blind, Parallel Group Comparison Study and Subsequent Open-label Study of GSK548470 in Patients With Compensated Chronic Hepatitis B Untreated With Nucleic Acid Analogue

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
166

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Aichi, Japan, 467-8602
        • GSK Investigational Site
      • Aichi, Japan, 466-8560
        • GSK Investigational Site
      • Chiba, Japan, 260-8677
        • GSK Investigational Site
      • Fukui, Japan, 918-8503
        • GSK Investigational Site
      • Fukuoka, Japan, 812-8582
        • GSK Investigational Site
      • Fukuoka, Japan, 820-8505
        • GSK Investigational Site
      • Fukuoka, Japan, 803-8505
        • GSK Investigational Site
      • Fukuoka, Japan, 810-8539
        • GSK Investigational Site
      • Gifu, Japan, 500-8717
        • GSK Investigational Site
      • Hiroshima, Japan, 734-8530
        • GSK Investigational Site
      • Hyogo, Japan, 663-8501
        • GSK Investigational Site
      • Hyogo, Japan, 651-2273
        • GSK Investigational Site
      • Kagawa, Japan, 760-8557
        • GSK Investigational Site
      • Kagoshima, Japan, 892-8512
        • GSK Investigational Site
      • Kagoshima, Japan, 890-8520
        • GSK Investigational Site
      • Kanagawa, Japan, 213-8587
        • GSK Investigational Site
      • Kumamoto, Japan, 862-8655
        • GSK Investigational Site
      • Miyagi, Japan, 980-8574
        • GSK Investigational Site
      • Miyazaki, Japan, 880-0003
        • GSK Investigational Site
      • Nagasaki, Japan, 852-8501
        • GSK Investigational Site
      • Nagasaki, Japan, 856-8562
        • GSK Investigational Site
      • Nara, Japan, 630-8305
        • GSK Investigational Site
      • Okayama, Japan, 700-0913
        • GSK Investigational Site
      • Okayama, Japan, 700-8511
        • GSK Investigational Site
      • Osaka, Japan, 540-0006
        • GSK Investigational Site
      • Osaka, Japan, 564-0013
        • GSK Investigational Site
      • Saga, Japan, 840-8571
        • GSK Investigational Site
      • Tokyo, Japan, 162-8655
        • GSK Investigational Site
      • Tokyo, Japan, 180-8610
        • GSK Investigational Site
      • Tokyo, Japan, 105-8471
        • GSK Investigational Site
      • Tokyo, Japan, 105-8470
        • GSK Investigational Site
      • Tokyo, Japan, 140-8522
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

16 years to 69 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • The ability to understand and sign a written informed consent form
  • 16 to 69 years of age at the time of informed consent
  • Females of childbearing potential must have a negative pregnancy test and agree to avoidance of pregnancy
  • Subject must show QTc < 450 millisecond (msec) or < 480 msec with Bundle Branch Block
  • Chronic HBV infection, defined as positive serum HBsAg for at least 6 month, or negative serum IgM-HBc antibody
  • HBeAg positive; HBV-DNA >= 6 log10 copies/mL, HBeAg negative; HBV-DNA >= 5 log10 copies/mL
  • Serum ALT >= 31 U/L and <= 10 × ULN
  • Creatinine clearance >= 70 mL/min
  • Haemoglobin >= 8 g/dL
  • WBC >= 1,000 /mm3
  • Nucleic acid analogue naïve, i.e., no prior therapy for over 6 months in the past
  • No mutation that shows resistance in LAM, ETV and/or TDF at screening

Exclusion Criteria:

  • Decompensated liver disease
  • Co-infection with HIV or HCV
  • Autoimmune hepatitis rather than chronic hepatitis B
  • Subject with serious complication
  • Received or have a plan for solid organ or bone marrow transplantation
  • Has proximal tubulopathy
  • History of hypersensitivity to nucleoside and/or nucleotide analogues
  • Evidence of hepatocellular carcinoma by diagnostic imaging at screening and/or serum α-fetoprotein > 50 ng/mL at screening
  • History of HCC
  • Received any nucleoside, nucleotide, interferon or HB vaccine therapy within 24 weeks prior to initiation
  • Received overdose NSAIDs, excluding temporary or topical use, within 7 days prior to initiation
  • Received drugs for injection containing glycyrrhizin as the main component within 4 weeks prior to initiation
  • Received drugs causing renal impairment, competitors of renal excretion, immunosuppressants, chemotherapeutics and/or corticosteroids within 8 weeks prior to initiation
  • Participation in another clinical study within 6 months of study entry or planned participation in another clinical study after entry to this study
  • Woman who is pregnant, lactating, possibly pregnant or planning a pregnancy during the study period
  • Psychiatry disorder or cognitive disorder that may affect the subject ability to give informed consent or to follow specified study procedures
  • History of alcohol or drug abuse
  • Any condition or situation that may interfere with the subject's participation in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: GSK548470 300 mg
GSK548470 300 mg tablet and ETV placebo capsule are administered once daily
Drug: GSK548470 300 mg tablet
Blue tablets, each tablet containing 300 mg of tenofovir disoproxil fumarate
Other Names:
  • GSK548470
ACTIVE_COMPARATOR: ETV 0.5 mg
ETV 0.5 mg capsule and GSK548470 placebo tablet are administered once daily
Drug: ETV 0.5 mg capsule
Brown capsules, each capsule containing 0.53 mg of entecavir hydrate
Other Names:
  • ETV

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline and Week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Baseline, Week 48 and Week 96
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.
Week 24, Week 48 and Week 96
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.
Week 24, Week 48 and Week 96
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.
Week 24, Week 48 and Week 96
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.
Week 24, Week 48 and Week 96
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.
Week 24, Week 48 and Week 96
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.
Week 24, Week 48 and Week 96
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.
Baseline, Week 24, Week 48 and Week 96
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.
Baseline, Week 24, Week 48 and Week 96
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.
From Baseline to throughout study
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), Adefovir dipivoxil (ADV), and/or ETV in a case where a virologic breakthrough has been observed after starting the study treatment (serum HBV DNA level has increased from the nadir by at least 1 log10 copies/mL) or where the serum HBV DNA level is not less than the HBV DNA detection limit (2.1 log10 copies/mL) at Week 24, Week 48 and Week 96. Virologic breakthrough was defined as 1.0 log10 or greater increases in serum HBV-DNA levels from on-treatment nadir. Participants who achieved the HBV-DNA values below lower limit of quantification (LLQ) (< 2.1 log10 copies/mL) in quantitative analysis at entire the study were also considered "Negative" in drug-resistance without implementation of genotypic analysis. Resistance mutation values were presented from Baseline to throughout the study. Baseline is defined as the value at Week 0 visit.
Screening, Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to throughout the study)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2011

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2013

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 23, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 23, 2011

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 28, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 10, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 7, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 115409

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