• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

Table E15Ongoing interventional randomized studies in patients with chronic hepatitis B (underlined outcomes assessment in patient subpopulations relevant to question 3)

SponsorIDTested DrugDesignOutcomes
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health Clinical Center (CC)NCT00023309Adefovir DipivoxilPhase 2, Randomized, Open Label, Parallel Assignment, Safety/Efficacy StudyMaintained combined response (virological, biochemical and histological response).
Loss of HBeAg, individual responses (virological, biochemical and histological), antiviral resistance and improvement in symptom scores
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health Clinical Center (CC)NCT00524173Tenofovir Disoproxil Fumarate Alone vs. Its Combination With EmtricitabinePhase 2, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudyMaintained suppression of HBV DNA below 102 copies/ml (<95 IU/ml, undetectable by current PCR-based assays, Roche Amplicor assay).
Normalization of ALT levels and histological improvements which are expected to occur in all patients with full suppression of HBV DNA and in a proportion of those with partial suppression; loss of HBeAg and loss of HBsAg
Foundation for Liver ResearchEudraCT: 2004-004736-30Peginterferon Alfa-2a and Ribavirin Combination
(HBeAg-Negative Chronic HBV Infection (PARC Study)
Phase 3, Randomized, Double Blind (Subject, Investigator), Placebo Control, Factorial Assignment, Efficacy StudyThe combined presence of HBV DNA level <10E4 copies/ml and ALT normalization at the end of followup
ALT normalization; HBV DNA negativity (undetectable by Taqman PCR)
HBsAg loss; Improvement liver histology; combined virological, biochemical and histological response
Achillion PharmaceuticalsNCT00040144ACH126, 433 (b-L-Fd4C)Phase 2, Randomized, Double-Blind, Dose Comparison, Parallel Assignment, Safety/Efficacy StudyNot reported
Bristol-Myers Squibb AdministrationNCT00065507Adefovir
Entecavir
Phase 3, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudyMean serum HBV DNA PCR adjusted for baseline levels
Discontinuation or dose reduction of study drug due to clinical AE or lab abnormality. Confirmed nephrotoxicity (increase in serum creatinine compared w/ baseline)
NovartisNCT00076336LamivudinePhase 3, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy StudyComposite endpoint termed Clinical Response, defined as three efficacy criteria: Serum HBV DNA < 4 log10 copies/mL, Normal ALT level, Improvement or stabilization in CTP score
NovartisNCT00076336TelbivudinePhase 3, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy StudyTime to Clinical Response; Duration of Clinical Response; Improvement, Stabilization, and Worsening in CTP score; Improvement, Stabilization, and Worsening in a modified (3-component) CTP score
National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Child Health and Human Development (NICHD)NCT00111943Tenofovir gelPhase 2, Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety StudyMacroscopic evidence of damage to the cervical, vulvar, or vaginal epithelium, including ulceration and other lesions, severe erythema, or severe edema, related or not related to the study gel or applicator
Adherence to the study gel regimen, acceptability of the study gel
GileadNCT00116805Adefovir dipivoxil
Tenofovir disoproxil fumarate
Phase III, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy StudyHBV DNA <400 copies/mL and histological improvement (at least a 2 point reduction in the Knodell necroinflammatory score without worsening in fibrosis)
HBV DNA <400 copies/mL
Histological improvement
ALT normalization
HBeAg and HBsAg loss/seroconversion
Development of resistance mutations
safety and tolerability
Gilead SciencesNCT00117676Adefovir dipivoxil
tenofovir disoproxil fumarate
Phase III, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy StudyHBV DNA <400 copies/mL and Histological Improvement (2 point reduction in Knodell Necroinflammatory score without worsening in Knodell fibrosis score)
Histological Improvement
Development of resistance mutations
Safety and Tolerability
ALT normalization
Idenix Pharmaceuticals; NovartisNCT00128544Telbivudine
Valtorcitabine
Phase 2, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy StudyNot reported
University Hospital, Bonn; Hoffmann-La RocheNCT00221286Pegylated interferon alfa 2a
pegylated interferon alfa 2a + tenofovir + emtricitabine
tenofovir + emtricitabine
Phase 3, Randomized, Open Label, Active Control, Factorial Assignment, Safety/Efficacy StudyHBeAg seroconversion
Study discontinuation due to adverse events
Loss of HBe-Ag; HBV-DNA < 5×103 copies/ml, (COBAS TaqMan HBV Test); decrease of HBV-DNA >2×log10 compared to baseline; normalization of ALT; Viral kinetics of HBV-DNA; Paired liver biopsy comparison according to METAVIR-activity and fibrosis score.
HIV-RNA <50 copies/ml and CD4-cell increase
Safety: number of adverse events, according to type and severity.
MTmedical Institute of Health
The University of Texas Health Science Center at San Antonio
BioMonde Preparations Limited
NCT002255374-Methylumbelliferone (Heparvit®)Phase 2, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Safety/Efficacy StudyReduction of virus in blood to undetectable levels;
Normalization of serum ALT and AST.
Reduced viral loads; Improvement of serum ALT and AST;
Improvement in general health status;
Improvement in serum marker of hepatic fibrosis;
Loss of HBeAg/seroconversion to HBeAb (for HBV patients).
Chinese University of Hong Kong; GlaxoSmithKlineNCT00226447Lamivudine
Pegylated Interferon
Phase 2, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy StudyHBV DNA reduction
Normalization of ALT and negative HBV DNA at EOT, negative HBV DNA at EOT; Safety of treatment
PowderMedNCT00277576HBV DNA Vaccine ppdpSC18Phase 1, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Safety StudyAdverse events at all visits, vaccine site evaluations, laboratory parameters pre and post vaccination
Seoul National University Hospital; Hoffmann-La RocheNCT00291616Pegylated Interferon-alpha 2a
Thymosin alpha 1
Phase 4, Randomized, Open Label, Historical Control, Parallel Assignment, Safety/Efficacy StudyHBeAg seroconversion, HBV DNA titer <20,000 IU/mL
Normalization of serum ALT, loss of HBeAg and HBsAg, production of anti-HBs
Gilead SciencesNCT00298363Emtricitabine
Entecavir
tenofovir disoproxil fumarate
Phase 2, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy StudySafety (adverse events and laboratory tests, discontinuations due to adverse events)
Thomas Jefferson UniversityNCT00307242Adefovir DipivoxilPhase 4, Randomized, Open Label, Active Control, Parallel Assignment, Safety StudyALT elevations (>10 × ULN); serum HBV DNA levels over time; serum ALT levels; YMDD variants; safety
Gilead SciencesNCT00307489Emtricitabine
Tenofovir DF
Phase 2, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Single Group Assignment, Safety/Efficacy StudyHBV DNA <169 copies/mL
Bukwang Pharmaceutical; Hong Kong: Department of HealthNCT00362635ClevudinePhase 3, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy StudyHBV DNA negativity (i.e., <300 copies/ml) by PCR
Safety: Laboratory tests, Adverse Events, Physical examination
Viral kinetics of HBV DNA suppression
Bristol-Myers Squibb; Korea: Food and Drug AdministrationNCT00393484Entecavir + Lamivudine PlaceboPhase 4, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Efficacy StudyUndetectable HBV DNA, <300 copies/mL, by Roche COBAS Amplicor PCR assay
Mean log10 reduction from baseline in HBV DNA; normalization of serum ALT (≤1 × ULN); HBV DNA < 103, <104 or <105 copies/mL
NovartisNCT00409019Adefovir
Telbivudine
Tenofovir
Phase IV, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy StudyNot reported
Bristol-Myers SquibbNCT00410072Entecavir
Entecavir + Tenofovir
Phase 3, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudyHBV DNA <50 IU/mL (approximately 300 copies/mL)
HBV DNA <50 IU/mL (300 copies/mL);
Mean Log 10 reduction from baseline in HBV DNA by PCR; ALT Normalization (≤1 × upper limit of normal); HBeAg loss; HBe seroconversion; HBs seroconversion
Frequency of adverse events, serious adverse events, and discontinuations from study drug due to adverse events or laboratory abnormalities
Bristol-Myers SquibbNCT00410202Entecavir vs. Adefovir Plus Lamivudine vs. Combination Entecavir Plus Adefovir in Lamivudine-Resistant Chronic Hepatitis B Subjects: The DEFINE StudyPhase 3, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudyHBV DNA <50 IU/mL (approximately 300 copies/mL)
Mean Log10 reduction from baseline in HBV DNA; ALT normalization (≤1 × upper limit of normal); HBeAg loss; HBe seroconversion; HBs seroconversion; virologic rebound due to genotypic resistance
Frequency of adverse events, serious adverse events, and discontinuations from study drug due to adverse events or laboratory abnormalities
Novartis; Idenix PharmaceuticalsNCT00412529Entecavir
Telbivudine
Phase 3, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudyChange in mean hepatitis B virus (HBV) DNA level from baseline; early viral kinetics through estimation of various parameters; change in ALT levels; the area under the curve (AUC) of HBV DNA change from baseline to week 12; polymerase chain reaction (PCR) negative;
Safety assessed by adverse events and laboratory values
Hoffmann-La RocheNCT00435825Peginterferon alfa 2aPhase 4, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy StudyHBeAg seroconversion
Loss of HBeAg, HBsAg seroconversion, loss of HBsAg, ALT, HBV-DNA
AEs, laboratory parameters
Hoffmann-La Roche; Bulgaria: Bulgarian Drug AgencyNCT00442572Peginterferon alfa 2aPhase 2, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudySerum HBV DNA <100,000 copies/mL
Loss of HBsAg and seroconversion
Changes in liver fibrosis, AEs, lab parameters
Gilead Sciences; United States: Food and Drug AdministrationNCT00507507Tenofovir disoproxil fumaratePhase 2, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy StudySuppression of HBV DNA <169 copies/mL
Gilead SciencesNCT00507689Emtricitabine/tenofovir disoproxil fumarate
Emtricitabine/tenofovir disoproxil fumarate + Hepatitis B Immunoglobulin
Phase 2, Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudyRecurrence of Chronic Hepatitis B virus post liver transplant
Genexine Co., Ltd.; Korea: Food and Drug AdministrationNCT00513968AdefovirPhase 1, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudyAdverse events and clinical laboratory abnormalities; HBeAg/HBsAg seroconversion rate, HBV Ag specific T cell immunity
Korea University; GlaxoSmithKlineNCT00531167Entecavir
Lamivudine + Adefovir
Phase 4, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy StudyPCR negativity (<60 IU/ml) of HBV DNA
1. PCR negativity (<60 IU/ml) of HBV DNA at year 1 (interim analysis) 2. Degrees of HBV DNA reduction 3. ALT normalization 4. HBeAg seroconversion 5. Development of resistant mutation 6. Virologic breakthrough 7. Biochemical breakthrough
Schering-Plough; China: State Food and Drug AdministrationNCT00536263Pegylated interferon alpha-2bPhase 3, Randomized, Open Label, Active Control, Crossover AssignmentHBeAg Loss; HBe seroconversion; HBV-DNA decrease; ALT normalization
Combined Response (defined as HBV DNA (PCR) <20,000 IUs/ml and HBe seroconversion and ALT normalization)
HBsAg Loss; HBs seroconversion
French National Agency for Research on AIDS and Viral HepatitisNCT00536627Naked DNA vaccine pCMVS2.SPhase 1/Phase 2, Randomized, Open Label, Parallel Assignment, Safety/Efficacy StudyVirologic failure defined by 1) reactivation after analogs' treatment interruption, 2) virologic breakthrough during treatment with analogs, 3) the impossibility for the patients to interrupt treatment at week 48
National Taiwan University Hospital; Bristol-Myers SquibbNCT00597259Entecavir
Pegasys plus Entecavir
Phase 4, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy StudyHBeAg seroconversion
Serum ALT normalization, HBeAg loss, serum HBV DNA disappearance, HBsAg disappearance, histological change, Entecavir resistance
Bristol-Myers SquibbNCT00605384Adefovir +Lamivudine
Entecavir + Tenofovir
Phase 3, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudyHBV DNA level <50 IU/mL
Hoffmann-La Roche; China: State Food and Drug AdministrationNCT00614471Entecavir
peginterferon alfa-2a
Phase 4, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudyLog change in quantitative HBeAg from baseline
HBeAg seroconversion, HBV-DNA <1000 copies/mL, loss of HBeAg, HBV DNA reduction, ALT normalization, loss of HBsAg seroconversion, reduction of HBsAg 24 weeks after end of treatment; AEs, laboratory parameters
Pusan National University Hospital; Yonsei UniversityNCT00625339Entecavir
Lamivudine
Phase 4, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudyHBV DNA <60 IU/mL (Undetectable serum HBV DNA by PCR method); drug resistant mutations; ALT normalization, HBeAg loss, HBe seroconversion, HBsAg loss and HBs seroconversion
Cumulative discontinuation rates due to lamivudine or entecavir resistance mutations and clinical breakthrough, Safety assessment
Yonsei University; Pusan National University Hospital; Yonsei UniversityNCT00625560Entecavir
Lamivudine
Phase 4, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudyHBV DNA < 60 IU/mL
Drug resistant mutations; change from baseline in mean HBV DNA; ALT normalization, HBeAg loss, HBe seroconversion, HBsAg loss and HBs seroconversion
Cumulative discontinuation rates due to lamivudine or entecavir resistance mutations and clinical breakthrough Safety assessment
Yonsei University; Pusan National University HospitalNCT00637663Entecavir
Lamivudine
Phase 4, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudyHBV DNA <60 IU/mL (Undetectable serum HBV DNA by PCR method); ALT normalization, HBeAg loss, HBe seroconversion, HBsAg loss and HBs seroconversion
Cumulative discontinuation rates due to lamivudine or Entecavir resistance mutations and clinical breakthrough, Safety assessment
Bukwang Pharmaceutical; South Korea: Korea Food and Drug Administration (KFDA)NCT00641082Adefovir
Clevudine
Phase 4, Randomized, Double-Blind, Parallel Assignment, Safety/Efficacy StudyHBV DNA below 300copies/mL
The change of HBV DNA from the baseline;
HBV DNA below LOD of RT-PCR; ALT normalization rate; viral breakthrough
Hoffmann-La Roche; Turkey: Ministry of HealthNCT00661076Adefovir dipivoxil
Peginterferon alfa-2a
Phase 3, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy StudyNormalization of ALT, and HBV-DNA <400 copies/mL
HBsAg quantitative loss and anti-HBs seroconversion; AEs, lab parameters, vital signs
University of Ulm; NovartisNCT00710216Lamivudine
Telbivudine
Phase 4, Randomized, Open Label, Active Control, Parallel Assignment, Pharmacokinetics/Dynamics StudyDecrease in viral load after 2 weeks of therapy measured in serum HBV-DNA concentration (Copies/ml or IU/ml)
Influence of HBeAg status to the decrease in viral load
Influence of HBV genotype to the decrease in viral load
Change in ALT and AST levels from baseline to week 12
Development of viral resistance and treatment failure during the study and subsequent course of observation
Safety assessed by adverse events and laboratory values
Maimonides Medical CenterNCT00715715Prednisone PrimingRandomized, Single Blind (Subject), Placebo Control, Parallel Assignment, Safety/Efficacy StudyReduction in HBV DNA, HBeAg seroconversion, normalization of ALT; histological improvement
Bristol-Myers Squibb; China: State Food and Drug AdministrationNCT00718887Adefovir, then Entecavir
Entecavir
Phase 4, Randomized, Open Label, Active Control, Crossover Assignment, Safety/Efficacy StudyHBV DNA <50 IU/mL
Mean reduction of HBV DNA; ALT normalization; HBeAg loss, seroconversion, HBsAg loss and seroconversion
Safety
Resistance
Gilead SciencesNCT00734162Tenofovir disoproxil fumaratePhase 2/Phase 3, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy StudyComposite endpoint of HBV DNA <400 copies/mL and ALT normal
Adverse events and clinical laboratory tests
Gilead SciencesNCT00737568Emtricitabine/tenofovir DF
Tenofovir DF
Phase 4, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy StudyAntiviral efficacy against HBV; safety and tolerability

From: Appendix E Tables and Figures

Cover of Management of Chronic Hepatitis B
Management of Chronic Hepatitis B.
Evidence Reports/Technology Assessments, No. 174.
Wilt TJ, Shamliyan T, Shaukat A, et al.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.