Phase 3 Completed N=166 Randomized Quadruple-blind Treatment

Phase 3 Study of GSK548470 in Patients With Compensated Chronic Hepatitis B Untreated With Nucleic Acid Analogue

Hepatitis B, Chronic

Source: ClinicalTrials.gov NCT01480284 ↗

Enrolled (actual)

166

Serious AEs

5.5%

Results posted

Oct 2013

Primary outcomePrimary: Mean Change From Baseline in Serum HBV DNA Level at Week 24 — -4.63; -4.50 log10 copies/milliliter (copies/mL) — p=<0.0001

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Mean Change From Baseline in Serum HBV DNA Level at Week 24	-4.63; -4.50	<0.0001 sig
SECONDARY Mean Change From Baseline in Serum HBV DNA Level at Week 48 and Week 96	-4.86; -4.85; -4.96; NA	—
SECONDARY Number of Participants With Serum HBV DNA < 2.1 log10 Copies/mL at Week 24, Week 48 and Week 96	59; 22; 84; 37; 97; NA	—
SECONDARY Number of Participants With Alanine Aminotransferase (ALT) Normalization at Week 24, Week 48 and Week 96	58; 35; 62; 35; 74; NA	—
SECONDARY Number of Participants With HBeAg Loss at Week 24, Week 48 and Week 96	3; 2; 9; 3; 13; NA	—
SECONDARY Number of Participants With HBeAg/HBeAb Seroconversion at Week 24, Week 48 and Week 96	0; 1; 4; 2; 5; NA	—
SECONDARY Number of Participants Achieving HBsAg Loss at Week 24, Week 48 and Week 96	0; 0; 0; 0; 1; NA	—
SECONDARY Number of Participants Achieving HBsAg/HBsAb Seroconversion at Week 24, Week 48 and Week 96	0; 0; 0; 0; 1; NA	—
SECONDARY Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96	2; 2; 15; 10; 58; 33	—
SECONDARY Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96	7; 0; 13; 6; 19; 11	—
SECONDARY Number of Participants With Virological Breakthrough Through End of the Study	2; 2	—
SECONDARY Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study)	0; 0; 0; 0; 0; 0	—

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 = 6 log10 copies/mL, HBeAg negative; HBV-DNA >= 5 log10 copies/mL
Serum ALT >= 31 U/L and = 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01480284). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.