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Hepatitis B, ChronicPhase 3NCT01475851

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

A Phase 3 study testing GSK548470 300 mg tablet in people with Hepatitis B, Chronic, run by GlaxoSmithKline at 11 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 once-daily treatment with GSK548470 300 mg in Japanese patients with compensated chronic hepatitis B with poor response to other drugs. 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
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
11 sitesJapan
Study dates
Dec 2011to Oct 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 <480msec with Bundle Branch Block
  • Chronic HBV infection, defined as positive serum HBsAg for at least 6 month
  • Subjects currently treated with LAM/ADV, ETV or ETV/ADV for greater than 24 weeks
Show all 11Show fewer
  • Chronic hepatitis B ; HBV NDA >= 4 log10 copies/mL, Chronic hepatitis B with cirrhosis ; HBV NDA >= 3 log10 copies/mL
  • Serum ALT <= 10 × ULN
  • Creatinine clearance >= 70 mL/min
  • Haemoglobin >= 8 g/dL
  • WBC >= 1,000 /mm3

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 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

11 sites in 1 country.

11 sites in 1 country

Japan11 sites

  • GSK Investigational Site

    Aichi, 466-8560

  • GSK Investigational Site

    Aichi, 467-8602

  • GSK Investigational Site

    Chiba, 260-8677

  • GSK Investigational Site

    Fukuoka, 803-8505

  • GSK Investigational Site

    Hiroshima, 734-8551

  • GSK Investigational Site

    Hokkaido, 060-0033

  • GSK Investigational Site

    Kagoshima, 890-8520

  • GSK Investigational Site

    Kanagawa, 213-8587

  • GSK Investigational Site

    Miyagi, 980-8574

  • GSK Investigational Site

    Tokyo, 105-8470

  • GSK Investigational Site

    Tokyo, 180-8610

Other trials in Japan

About this study

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

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.

Read the detailed description

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.

Being tested
GSK548470 300 mg tablet
Keywords
Tenofovir disoproxil fumarate, compensated 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 containing 300 mg of tenofovir disoproxil fumarate

Study groups in NCT01475851
Study groupRoleWhat they receive
GSK548470 300 mgExperimentalGSK548470 300 mg tablet is administered orally once daily
Receives: Drug: GSK548470 300 mg tablet

What is being measured

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

  1. Number of Participants With HBV DNA Level < 2.1 log10 Copies/mL at 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.

    Measured: Week 24

Secondary outcomes (10)

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

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

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

    Measured: 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 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.

    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 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.

    Measured: Week 24, Week 48 and Week 96

  8. Number of Participants With Virological Breakthrough and Resistance-related Mutations

    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.

    Measured: Screening, Week 24, Week 48, Week 96 and Virological Breakthrough

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

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

  10. 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 log10, 3.0 to 4.0 log10, 4.0 to 5.0 log10, 5.0 to 6.0 log10, >=6.0 log10) (kilo units 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

Timeline

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

  1. First posted21 Nov 2011 (estimated)
  2. Study startDec 2011
  3. Primary completionJun 2013
  4. Study completionOct 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01475851
Sponsor's protocol ID
115912
Status last verified
May 2015
First submitted
17 Nov 2011
Last updated
22 Jun 2015
Data monitoring committee
No

Publications

  • Kumada H, Koike K, Suyama K, Ito H, Itoh H, Sugiura W. Efficacy and safety of tenofovir disoproxil fumarate rescue therapy for chronic hepatitis B patients who failed other nucleos(t)ide analogs. Hepatol Res. 2017 Sep;47(10):1032-1041. doi: 10.1111/hepr.12842. Epub 2016 Dec 21.

    PubMed 27862721

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing GSK548470 300 mg tablet in people with Hepatitis B, Chronic, run by GlaxoSmithKline at 11 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 11 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 22 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 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 4 Nov 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?

Number of Participants With HBV DNA Level < 2.1 log10 Copies/mL at Week 24 (time frame: 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 NCT01475851, 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 22 Jun 2015.

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