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
Completed
Completed
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:
Drug: GSK548470 300 mg tablet
Drug: ETV 0.5 mg capsule
Enrollment:
166
Observational study model:
Not applicable
Primary completion date:
2013-10-01
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
Completed
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
Participate in clinical trial
Access to clinical trial data by researchers
Visit website