- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01480284
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
Completed
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
166
Phase
- 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
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Aichi, Japan, 467-8602
- GSK Investigational Site
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Aichi, Japan, 466-8560
- GSK Investigational Site
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Chiba, Japan, 260-8677
- GSK Investigational Site
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Fukui, Japan, 918-8503
- GSK Investigational Site
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Fukuoka, Japan, 812-8582
- GSK Investigational Site
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Fukuoka, Japan, 820-8505
- GSK Investigational Site
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Fukuoka, Japan, 803-8505
- GSK Investigational Site
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Fukuoka, Japan, 810-8539
- GSK Investigational Site
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Gifu, Japan, 500-8717
- GSK Investigational Site
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Hiroshima, Japan, 734-8530
- GSK Investigational Site
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Hyogo, Japan, 663-8501
- GSK Investigational Site
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Hyogo, Japan, 651-2273
- GSK Investigational Site
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Kagawa, Japan, 760-8557
- GSK Investigational Site
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Kagoshima, Japan, 892-8512
- GSK Investigational Site
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Kagoshima, Japan, 890-8520
- GSK Investigational Site
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Kanagawa, Japan, 213-8587
- GSK Investigational Site
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Kumamoto, Japan, 862-8655
- GSK Investigational Site
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Miyagi, Japan, 980-8574
- GSK Investigational Site
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Miyazaki, Japan, 880-0003
- GSK Investigational Site
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Nagasaki, Japan, 852-8501
- GSK Investigational Site
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Nagasaki, Japan, 856-8562
- GSK Investigational Site
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Nara, Japan, 630-8305
- GSK Investigational Site
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Okayama, Japan, 700-0913
- GSK Investigational Site
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Okayama, Japan, 700-8511
- GSK Investigational Site
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Osaka, Japan, 540-0006
- GSK Investigational Site
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Osaka, Japan, 564-0013
- GSK Investigational Site
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Saga, Japan, 840-8571
- GSK Investigational Site
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Tokyo, Japan, 162-8655
- GSK Investigational Site
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Tokyo, Japan, 180-8610
- GSK Investigational Site
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Tokyo, Japan, 105-8471
- GSK Investigational Site
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Tokyo, Japan, 105-8470
- GSK Investigational Site
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Tokyo, Japan, 140-8522
- GSK Investigational Site
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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
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 |
Intervention / Treatment |
---|---|
EXPERIMENTAL: GSK548470 300 mg
GSK548470 300 mg tablet and ETV placebo capsule are administered once daily
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Blue tablets, each tablet containing 300 mg of tenofovir disoproxil fumarate
Other Names:
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ACTIVE_COMPARATOR: ETV 0.5 mg
ETV 0.5 mg capsule and GSK548470 placebo tablet are administered once daily
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Brown capsules, each capsule containing 0.53 mg of entecavir hydrate
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Change From Baseline in Serum HBV DNA Level at Week 24
Time Frame: Baseline and Week 24
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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.
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Baseline and Week 24
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Secondary Outcome Measures
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
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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.
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Baseline, Week 48 and Week 96
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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
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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.
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Week 24, Week 48 and Week 96
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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
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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.
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Week 24, Week 48 and Week 96
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Number of Participants With HBeAg Loss at Week 24, Week 48 and Week 96
Time Frame: Week 24, Week 48 and Week 96
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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.
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Week 24, Week 48 and Week 96
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Number of Participants With HBeAg/HBeAb Seroconversion at Week 24, Week 48 and Week 96
Time Frame: Week 24, Week 48 and Week 96
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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.
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Week 24, Week 48 and Week 96
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Number of Participants Achieving HBsAg Loss at Week 24, Week 48 and Week 96
Time Frame: Week 24, Week 48 and Week 96
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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.
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Week 24, Week 48 and Week 96
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Number of Participants Achieving HBsAg/HBsAb Seroconversion at Week 24, Week 48 and Week 96
Time Frame: Week 24, Week 48 and Week 96
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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.
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Week 24, Week 48 and Week 96
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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
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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.
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Baseline, Week 24, Week 48 and Week 96
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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
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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.
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Baseline, Week 24, Week 48 and Week 96
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Number of Participants With Virological Breakthrough Through End of the Study
Time Frame: From Baseline to throughout study
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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.
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From Baseline to throughout study
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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)
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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.
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Screening, Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to throughout the study)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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.
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
November 1, 2011
Primary Completion (ACTUAL)
January 1, 2013
Study Completion (ACTUAL)
November 1, 2014
Study Registration Dates
First Submitted
November 23, 2011
First Submitted That Met QC Criteria
November 23, 2011
First Posted (ESTIMATE)
November 28, 2011
Study Record Updates
Last Update Posted (ESTIMATE)
August 10, 2016
Last Update Submitted That Met QC Criteria
July 7, 2016
Last Verified
July 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Hepatitis, Chronic
Other Study ID Numbers
- 115409
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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