Clinical trial NCT01480284: Phase 3 Study of GSK548470 in Patients With Compensated Chronic Hepatitis B Untreated With Nucleic Acid Analogue
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis B, Chronic
Keywords: Tenofovir Disoproxil Fumarate
Chronic Hepatitis B
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-11-28
Enrollment: 166
Sex: ALL
Minimum age (years): 16
Maximum age (years): 69
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. In efficacy, the non-inferiority of GSK548470 to ETV will be verified using the antiviral effect as the index.

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.

Eligibility 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

Primary outcomes:
measure: Mean Change From Baseline in Serum HBV DNA Level at Week 24
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Mean Change From Baseline in Serum HBV DNA Level at Week 48 and Week 96
timeFrame: Baseline, Week 48 and Week 96
measure: 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
measure: Number of Participants With Alanine Aminotransferase (ALT) Normalization at Week 24, Week 48 and Week 96
timeFrame: Week 24, Week 48 and Week 96
measure: Number of Participants With HBeAg Loss at Week 24, Week 48 and Week 96
timeFrame: Week 24, Week 48 and Week 96
measure: Number of Participants With HBeAg/HBeAb Seroconversion at Week 24, Week 48 and Week 96
timeFrame: Week 24, Week 48 and Week 96
measure: Number of Participants Achieving HBsAg Loss at Week 24, Week 48 and Week 96
timeFrame: Week 24, Week 48 and Week 96
measure: Number of Participants Achieving HBsAg/HBsAb Seroconversion at Week 24, Week 48 and Week 96
timeFrame: Week 24, Week 48 and Week 96
measure: 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
measure: 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
measure: Number of Participants With Virological Breakthrough Through End of the Study
timeFrame: From Baseline to throughout study
measure: 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)
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Fukui
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Gifu
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kagoshima
country: Japan
facility: GSK Investigational Site
city: Kagoshima
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kumamoto
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Miyazaki
country: Japan
facility: GSK Investigational Site
city: Nagasaki
country: Japan
facility: GSK Investigational Site
city: Nagasaki
country: Japan
facility: GSK Investigational Site
city: Nara
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saga
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.