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Hepatitis B, ChronicPhase 3NCT01480284

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

A Phase 3 study testing GSK548470 300 mg tablet and ETV 0.5 mg capsule in people with Hepatitis B, Chronic, run by GlaxoSmithKline at 32 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 16 to 69 years
Conditions the study is for
Hepatitis B, Chronic
What is being tested?
GSK548470 300 mg tablet and ETV 0.5 mg capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
166 participants
Where
32 sitesJapan
Study dates
Nov 2011to Nov 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 69 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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

Trial locations and contacts

32 sites in 1 country.

32 sites in 1 country

Japan32 sites

  • GSK Investigational Site

    Aichi, 466-8560

  • GSK Investigational Site

    Aichi, 467-8602

  • GSK Investigational Site

    Chiba, 260-8677

  • GSK Investigational Site

    Fukui, 918-8503

  • GSK Investigational Site

    Fukuoka, 803-8505

  • GSK Investigational Site

    Fukuoka, 810-8539

  • GSK Investigational Site

    Fukuoka, 812-8582

  • GSK Investigational Site

    Fukuoka, 820-8505

  • GSK Investigational Site

    Gifu, 500-8717

  • GSK Investigational Site

    Hiroshima, 734-8530

  • GSK Investigational Site

    Hyōgo, 651-2273

  • GSK Investigational Site

    Hyōgo, 663-8501

  • GSK Investigational Site

    Kagawa, 760-8557

  • GSK Investigational Site

    Kagoshima, 890-8520

  • GSK Investigational Site

    Kagoshima, 892-8512

  • GSK Investigational Site

    Kanagawa, 213-8587

  • GSK Investigational Site

    Kumamoto, 862-8655

  • GSK Investigational Site

    Miyagi, 980-8574

  • GSK Investigational Site

    Miyazaki, 880-0003

  • GSK Investigational Site

    Nagasaki, 852-8501

  • GSK Investigational Site

    Nagasaki, 856-8562

  • GSK Investigational Site

    Nara, 630-8305

  • GSK Investigational Site

    Okayama, 700-0913

  • GSK Investigational Site

    Okayama, 700-8511

  • GSK Investigational Site

    Osaka, 540-0006

  • GSK Investigational Site

    Osaka, 564-0013

  • GSK Investigational Site

    Saga, 840-8571

  • GSK Investigational Site

    Tokyo, 105-8470

  • GSK Investigational Site

    Tokyo, 105-8471

  • GSK Investigational Site

    Tokyo, 140-8522

  • GSK Investigational Site

    Tokyo, 162-8655

  • GSK Investigational Site

    Tokyo, 180-8610

Other trials in Japan

About this study

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 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.

Read the 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.

Being tested
GSK548470 300 mg tablet, ETV 0.5 mg capsule
Keywords
Tenofovir Disoproxil Fumarate, Chronic Hepatitis B
Medical subject headings
Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK548470 300 mg tabletDrug

    Also called GSK548470

    Blue tablets, each tablet containing 300 mg of tenofovir disoproxil fumarate

  • ETV 0.5 mg capsuleDrug

    Also called ETV

    Brown capsules, each capsule containing 0.53 mg of entecavir hydrate

Study groups in NCT01480284
Study groupRoleWhat they receive
GSK548470 300 mgExperimentalGSK548470 300 mg tablet and ETV placebo capsule are administered once daily
Receives: Drug: GSK548470 300 mg tablet
ETV 0.5 mgActive comparatorETV 0.5 mg capsule and GSK548470 placebo tablet are administered once daily
Receives: Drug: ETV 0.5 mg capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Change From Baseline in Serum HBV DNA Level at 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.

    Measured: Baseline and Week 24

Secondary outcomes (11)

  1. Mean Change From Baseline in Serum HBV DNA Level at 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.

    Measured: Baseline, Week 48 and Week 96

  2. Number of Participants With Serum HBV DNA < 2.1 log10 Copies/mL at 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.

    Measured: Week 24, Week 48 and Week 96

  3. Number of Participants With Alanine Aminotransferase (ALT) Normalization at 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.

    Measured: Week 24, Week 48 and Week 96

  4. Number of Participants With HBeAg Loss at 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.

    Measured: Week 24, Week 48 and Week 96

  5. Number of Participants With HBeAg/HBeAb Seroconversion at 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.

    Measured: Week 24, Week 48 and Week 96

  6. Number of Participants Achieving HBsAg Loss at 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.

    Measured: Week 24, Week 48 and Week 96

  7. Number of Participants Achieving HBsAg/HBsAb Seroconversion at 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.

    Measured: Week 24, Week 48 and Week 96

  8. Number of Participants Achieving Each Indicated HBsAg Category at 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.

    Measured: Baseline, Week 24, Week 48 and Week 96

  9. Number of Participants Achieving Each Indicated HBcrAg Category at 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.

    Measured: Baseline, Week 24, Week 48 and Week 96

  10. Number of Participants With Virological Breakthrough Through End of the 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.

    Measured: From Baseline to throughout study

  11. Number of Participants With Resistance Related Mutations at 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.

    Measured: Screening, Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to throughout the study)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Nov 2011 (estimated)
  2. Study startNov 2011
  3. Primary completionJan 2013
  4. Study completionNov 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
166 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01480284
Sponsor's protocol ID
115409
Status last verified
Jul 2016
First submitted
23 Nov 2011
Last updated
10 Aug 2016
Data monitoring committee
No

Publications

  • Koike K, Suyama K, Ito H, Itoh H, Sugiura W. Randomized prospective study showing the non-inferiority of tenofovir to entecavir in treatment-naive chronic hepatitis B patients. Hepatol Res. 2018 Jan;48(1):59-68. doi: 10.1111/hepr.12902. Epub 2017 May 24.

    PubMed 28374496

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing GSK548470 300 mg tablet and ETV 0.5 mg capsule in people with Hepatitis B, Chronic, run by GlaxoSmithKline at 32 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline in Serum HBV DNA Level at Week 24 (time frame: Baseline and Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01480284, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2016.

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