Last updated: 11/07/2018 09:29:51
Phase 3 study of GSK548470 in patients with compensated chronic hepatitis B untreated with nucleic acid analogue
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Mean change from Baseline in serum HBV DNA level at Week 24
Timeframe: Baseline and Week 24
Secondary outcomes:
Mean change from Baseline in serum HBV DNA level at Week 48 and Week 96
Timeframe: 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
Timeframe: Week 24, Week 48 and Week 96
Number of participants with alanine aminotransferase (ALT) normalization at Week 24, Week 48 and Week 96
Timeframe: Week 24, Week 48 and Week 96
Number of participants with HBeAg loss at Week 24, Week 48 and Week 96
Timeframe: Week 24, Week 48 and Week 96
Number of participants with HBeAg/HBeAb seroconversion at Week 24, Week 48 and Week 96
Timeframe: Week 24, Week 48 and Week 96
Number of participants achieving HBsAg loss at Week 24, Week 48 and Week 96
Timeframe: Week 24, Week 48 and Week 96
Number of participants achieving HBsAg/HBsAb seroconversion at Week 24, Week 48 and Week 96
Timeframe: Week 24, Week 48 and Week 96
Number of participants achieving each indicated HBsAg category at Baseline, Week 24, Week 48 and Week 96
Timeframe: 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
Timeframe: Baseline, Week 24, Week 48 and Week 96
Number of participants with virological breakthrough through end of the study
Timeframe: 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)
Timeframe: Screening, Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to throughout the study)
Interventions:
Enrollment:
166
Primary completion date:
2013-10-01
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Kazuhiko Koike, Kazuaki Suyama, Hiroshi Ito, Hiroshi Itoh, Wataru Sugiura. A Randomized Prospective Study Showing the Non-inferiority of Tenofovir to Entecavir in Treatment-naïve Chronic Hepatitis B Patients. Hepatol Res. 2018;48(1):59-68
Medical condition
Hepatitis B, Chronic
Product
tenofovir disoproxil fumarate
Collaborators
Not applicable
Study date(s)
November 2011 to November 2014
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
16 - 69 years
Accepts healthy volunteers
No
- The ability to understand and sign a written informed consent form
- 16 to 69 years of age at the time of informed consent
- Decompensated liver disease
- Co-infection with HIV or HCV
Inclusion and exclusion criteria
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
Trial location(s)
Study documents
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2013-10-01
Actual study completion date
2014-19-11
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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