Clinical trial NCT01475851: Phase 3 Study of GSK548470 in Patients With Compensated Chronic Hepatitis B With Poor Response to Other Drugs
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis B, Chronic
Keywords: Tenofovir disoproxil fumarate, compensated chronic hepatitis B
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-11-21
Enrollment: 34
Sex: ALL
Minimum age (years): 16
Maximum age (years): 69
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

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 \<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
* 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

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 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: Number of Participants With HBV DNA Level < 2.1 log10 Copies/mL at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Mean Change From Baseline in Serum HBV DNA Level at Week 24, Week 48 and Week 96
timeFrame: Baseline and Week 24, Week 48 and Week 96
measure: Number of Participants With Serum HBV DNA < 2.1 log10 Copies/mL at Week 48 and Week 96
timeFrame: 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 With Virological Breakthrough and Resistance-related Mutations
timeFrame: Screening, Week 24, Week 48, Week 96 and Virological Breakthrough
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
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: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Kagoshima
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Miyagi
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: 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.