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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01480284
First received: November 23, 2011
Last updated: November 13, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis B, Chronic
Drug: GSK548470 300 mg tablet
Drug: ETV 0.5 mg capsule
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Mean Change From Baseline in Serum HBV DNA Level at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The mean change from Baseline in the hepatitis B virus deoxyribonucleic acid (HBV DNA) level at Week 24 was assessed (lower limit of quantitation : 2.1 log 10 copies/mL). The mean values were adjusted by Baseline HBV DNA levels. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.


Secondary Outcome Measures:
  • Mean Change From Baseline in Serum HBV DNA Level at Week 48 and Week 96 [ Time Frame: Baseline, Week 48 and Week 96 ] [ Designated as safety issue: No ]
  • Number of Participants With Serum HBV DNA <2.1 log10 Copies/mL at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The number of participants with serum HBV DNA level less than the lower limit of quantitation (i.e. 2.1 log10 copies/mL) at Week 24 was summarized.

  • Number of Participants With Alanine Aminotransferase (ALT) Normalization at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The number of participants with alanine aminotransferase (ALT) normalization at Week 24 were summarized. ALT normalization is defined as ALT exceed the upper limit of normal range at Baseline and within the normal range at Week 24.

  • Number of Participants With HBeAg Loss at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The number of participants achieving hepatitis B e antigen (HBeAg) loss at Week 24 in positive HBeAg participants at Baseline was summarized. Loss of HBeAg is defined as the change of detectable HBeAg from positive to negative.

  • Number of Participants With HBeAg/HBeAb Seroconversion at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The number of participants achieving hepatitis B e antigen (HBeAg)/hepatitis B e antibody (HBeAb) seroconversion at Week 24 in positive HBeAg and negative HBeAb participants at Baseline was summarized. Seroconversion to HBeAg is defined as change of detectable antibody to HBeAg from negative to positive.

  • Number of Participants Achieving HBsAg Loss at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The number of participants with hepatitis B surface antigen (HBsAg) loss at Week 24 in positive HBsAg participants at Baseline was summarized. Loss of HBsAg is defined as change of detectable HBsAg from positive to negative.

  • Number of Participants Achieving HBsAg/HBsAb Seroconversion at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The number of participants with hepatitis B surface antigen (HBsAg)/hepatitis B surface antibody (HBsAb) seroconversion at Week 24 in positive HBsAg and negative HBsAb participants at Baseline was summarized. HBsAg seroconversion .is defined as change of detectable antibody to HBsAg from negative to positive.

  • Number of Participants Achieving Each Indicated HBsAg Category at Baseline and Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The number of participants achieving each indicated hepatitis B surface antigen (HBsAg) category (HBsAg <80, 80 to 800, 800 to 8000, 8000 to 80000, and ≥80000) (kilo international unit per liter [KIU/L]) by study visit was summarized.

  • Number of Participants Achieving Each Indicated HBcrAg Category at Baseline and Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The number of participants achieving each indicated hepatitis B core-related antigen (HBcrAg) category (HBcrAg <3.0, 3.0 to 4.0, 4.0 to 5.0, 5.0 to 6.0, and ≥6.0) (Log kilo unit per liter [KU/L]) by study visit was summarized.

  • Number of Participants With Virological Breakthrough Through Weeks 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The number of participants who experienced virological breakthrough was summarized. Virological breakthrough is defined as serum HBV DNA level increase >=1 log10 copies/mL above the treatment nadir.

  • Number of Participants With Resistance Related Mutations at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The development of drug resistance-associated mutations was analyzed to look for resistance to Lamivudine (LAM), Adefovir dipivoxil (ADV), and/or ETV in a case where a virologic breakthrough has been observed after starting the study treatment (serum HBV DNA level has increased from the nadir by at least 1 log10 copies/mL) or where the serum HBV DNA level is not less than the HBV DNA detection limit (2.1 log10 copies/mL) at Week 24.


Enrollment: 166
Study Start Date: November 2011
Estimated Study Completion Date: December 2014
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK548470 300 mg
GSK548470 300 mg tablet and ETV placebo capsule are administered once daily
Drug: GSK548470 300 mg tablet
Blue tablets, each tablet containing 300 mg of tenofovir disoproxil fumarate
Other Name: GSK548470
Active Comparator: ETV 0.5 mg
ETV 0.5 mg capsule and GSK548470 placebo tablet are administered once daily
Drug: ETV 0.5 mg capsule
Brown capsules, each capsule containing 0.53 mg of entecavir hydrate
Other Name: ETV

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

Ages Eligible for Study:   16 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01480284

Locations
Japan
GSK Investigational Site
Aichi, Japan, 466-8560
GSK Investigational Site
Aichi, Japan, 467-8602
GSK Investigational Site
Chiba, Japan, 260-8677
GSK Investigational Site
Fukui, Japan, 918-8503
GSK Investigational Site
Fukuoka, Japan, 820-8505
GSK Investigational Site
Fukuoka, Japan, 803-8505
GSK Investigational Site
Fukuoka, Japan, 810-8539
GSK Investigational Site
Fukuoka, Japan, 812-8582
GSK Investigational Site
Gifu, Japan, 500-8717
GSK Investigational Site
Hiroshima, Japan, 734-8530
GSK Investigational Site
Hyogo, Japan, 663-8501
GSK Investigational Site
Hyogo, Japan, 651-2273
GSK Investigational Site
Kagawa, Japan, 760-8557
GSK Investigational Site
Kagoshima, Japan, 890-8520
GSK Investigational Site
Kagoshima, Japan, 892-8512
GSK Investigational Site
Kanagawa, Japan, 213-8587
GSK Investigational Site
Kumamoto, Japan, 862-8655
GSK Investigational Site
Miyagi, Japan, 980-8574
GSK Investigational Site
Miyazaki, Japan, 880-0003
GSK Investigational Site
Nagasaki, Japan, 852-8501
GSK Investigational Site
Nagasaki, Japan, 856-8562
GSK Investigational Site
Nara, Japan, 630-8305
GSK Investigational Site
Okayama, Japan, 700-0913
GSK Investigational Site
Okayama, Japan, 700-8511
GSK Investigational Site
Osaka, Japan, 540-0006
GSK Investigational Site
Osaka, Japan, 564-0013
GSK Investigational Site
Saga, Japan, 840-8571
GSK Investigational Site
Tokyo, Japan, 180-8610
GSK Investigational Site
Tokyo, Japan, 162-8655
GSK Investigational Site
Tokyo, Japan, 105-8471
GSK Investigational Site
Tokyo, Japan, 105-8470
GSK Investigational Site
Tokyo, Japan, 140-8522
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01480284     History of Changes
Other Study ID Numbers: 115409
Study First Received: November 23, 2011
Results First Received: August 22, 2013
Last Updated: November 13, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by GlaxoSmithKline:
Tenofovir Disoproxil Fumarate
Chronic Hepatitis B

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
DNA Virus Infections
Digestive System Diseases
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014