Back to resultsEffects of Telbivudine and Tenofovir Disoproxil Fumarate Treatment on the Hepatitis B Virus DNA Kinetics in CHB
Primary Purpose
Hepatitis B Virus
Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Telbivudine
Tenofovir
Telbivudine plus tenofovir
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis B Virus focused on measuring Chronic HBV, Asian adult subjects with chronic HBV, in immune tolerant phase, and positive for hepatitis B e antigen (HBeAg)
Eligibility Criteria
Inclusion Criteria:
- Chronic HBV infection, defined as positive serum HBsAg for at least 6 months, or HBsAg positive > 3 months and negative for IgM anti-HBc and positive for IgG anti-HBc
- Age < 40 years old
- HBeAg positive
- HBV DNA > or = to 10^7 copies/mL by Abbott real-time PCR
- ALT < or = to 1 ULN
- Willing and able to provide written informed consent
- No prior oral HBV therapy (e.g., nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)
- Is willing and able to comply with the study drug regimen and all other study procedures and requirements
- Is willing and able to provide written informed consent before any study assessment is perform
Exclusion Criteria:
- Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 × ULN, PT > 1.2 × ULN, platelets < 150,000/mm3, serum albumin < 3.5 g/dL, or prior history of clinical hepatic decompensation (e.g. ascites, jaundice, encephalopathy, variceal hemorrhage).
- Received interferon (pegylated or not) therapy within 6 months of the screening visit
- α-fetoprotein > 50 ng/mL
- Evidence of hepatocellular carcinoma (HCC)
- Co-infection with HCV (by serology), or HIV,
- Significant renal, cardiovascular, pulmonary, or neurological disease.
- Received solid organ or bone marrow transplantation.
- Is currently receiving therapy with immunomodulators (e.g., corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion.
- Has proximal tubulopathy.
- Use of other investigational drugs at the time of enrollment, or within 30 days
- History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
- Is pregnant or breastfeeding.
- Is a women of child-bearing potential (WOCBP)unless post-menopausal or using one or more acceptable method of contraception.
- Patient has any other concurrent medical or social condition likely to preclude compliance with the schedule of evaluations in the protocol, or likely to confound the efficacy or safety observations of the study.
- Patient is currently abusing alcohol or illicit drugs, or has a history of alcohol abuse or illicit substance abuse within the preceding two years.
- Patient has a medical condition that requires prolonged or frequent use of systemic acyclovir or famciclovir.
Other protocol-defined inclusion/exclusion criteria may apply
Sites / Locations
- Department of Medicine, Queen Mary Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
Telbivudine 600 mg monotherapy
Tenofovir disproxil fumarate 300 mg monotherapy
Telbivudine 600 mg and Tenofovir 300 mg
Arm Description
All patients in this arm were randomized to receive Telbivudine (LDT) 600 mg QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
All patients in this arm were randomized to receive Tenofovir disoproxil fumarate 300 mg(equivalent to tenofovir disoproxil 245 mg)QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
All patients in this arm were randomized to receive Telbivudine (LDT) 600 mg QD and Tenofovir (TDF) 300 mg (equivalent to Tenofovir disoproxil 245 mg)QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
Outcomes
Primary Outcome Measures
Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12.
Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA. Serum HBV DNA determinations were performed at a central laboratory through use of the COBAS TaqMan™ HBV DNA assay (Roche Molecular Systems, Pleasanton, CA, USA) which utilized the Real-time polymerase chain reaction (PCR) method and automated extraction by Cobas Ampliprep (threshold for detection 12 IU/mL). The Screening serum HBV DNA values must be ≥ 7 log10 copies/mL by COBAS TaqMan™ HBV DNA assay.
Secondary Outcome Measures
Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Weeks 2, 4 and 8.
Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA. Serum HBV DNA determinations were performed at a central laboratory through use of the COBAS TaqMan™ HBV DNA assay (Roche Molecular Systems, Pleasanton, CA, USA) which utilized the Real-time polymerase chain reaction (PCR) method and automated extraction by Cobas Ampliprep (threshold for detection 12 IU/mL). The Screening serum HBV DNA values must be ≥ 7 log10 copies/mL by COBAS TaqMan™ HBV DNA assay.
Percentage of Patients Who Are Polymerase Chain Reaction(PCR)Negative at Week 12
Polymerase Chain Reaction (PCR) Negative is defined as HBV DNA levels <25 copies/ml.
Percentage of Patients Who Achieve Hepatitis B "e" Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 12
HBeAg loss is defined as the loss of detectable serum HBeAg in a patient who was HBeAg positive at baseline. HBeAg seroconversion is defined as HBeAg loss with detectable Hepatitis B 'e' antibody (HBeAb). HBeAg stands for hepatitis B "e" antigen. This antigen is a protein from the hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the person is infectious and is able to spread the virus to other people.
Characterization of Very Early Viral Kinetics Through Estimated Viral Load
The underlying bi-phasic model of viral kinetics can be described as follows:
V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss
Characterization of Very Early Viral Kinetics Through Viral Clearance
The underlying bi-phasic model of viral kinetics can be described as follows:
V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss
Characterization of Very Early Viral Kinetics Through Rate of Infected Cell Loss
The underlying bi-phasic model of viral kinetics can be described as follows:
V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss
Characterization of Very Early Viral Kinetics Through Efficiency Factor of Blocking Virus Production.
The underlying bi-phasic model of viral kinetics can be described as follows:
V(t) (1 )pI(t) cV(t) I(t) (1 ) (T I(t))V(t) I(t) where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise allinfected and uninfected target cells, and δ the rate of infected cell loss
Characterization of Very Early Viral Kinetics Through Half-live of Free Virus
The underlying bi-phasic model of viral kinetics can be described as follows:
V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss
Full Information
NCT ID
NCT00805675
First Posted
December 9, 2008
Last Updated
January 26, 2012
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00805675
Brief Title
Effects of Telbivudine and Tenofovir Disoproxil Fumarate Treatment on the Hepatitis B Virus DNA Kinetics in CHB
Official Title
A Randomized, Open-label, Controlled, Exploratory Trial to Characterize the Results of Daily Oral Administration of Telbivudine 600 mg and Tenofovir Disproxil Fumarate 300 mg in Combination or Telbivudine 600 mg or Tenofovir Disproxil Fumarate 300 mg Monotherapy Given Over 12 Weeks on the Kinetics of Hepatitis B Virus DNA in Adults With HBeAg Positive Compensated CHB
Study Type
Interventional
2. Study Status
Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to compare the safety, tolerability and effectiveness of 12 weeks of treatment with telbivudine 600 mg daily plus tenofovir DF 300 mg one daily (OD) taken together vs. tenofovir DF 300 mg once daily (QD) or vs telbivudine 600 mg monotherapy daily (QD). This is an open labeled, active controlled, viral kinetics study which means the subjects and study doctor will know what study drug subjects have been assigned. This study is open to male and female subjects, <40 years of age, who have been infected with HBV for at least 6 months and have not received oral treatment for HBV.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B Virus
Keywords
Chronic HBV, Asian adult subjects with chronic HBV, in immune tolerant phase, and positive for hepatitis B e antigen (HBeAg)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
83 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Telbivudine 600 mg monotherapy
Arm Type
Experimental
Arm Description
All patients in this arm were randomized to receive Telbivudine (LDT) 600 mg QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
Arm Title
Tenofovir disproxil fumarate 300 mg monotherapy
Arm Type
Active Comparator
Arm Description
All patients in this arm were randomized to receive Tenofovir disoproxil fumarate 300 mg(equivalent to tenofovir disoproxil 245 mg)QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
Arm Title
Telbivudine 600 mg and Tenofovir 300 mg
Arm Type
Active Comparator
Arm Description
All patients in this arm were randomized to receive Telbivudine (LDT) 600 mg QD and Tenofovir (TDF) 300 mg (equivalent to Tenofovir disoproxil 245 mg)QD. Patients were randomized prior to the first dose of study medication, which was defined as the study Baseline (Day 1) Visit. Subsequently, patients returned to the clinic at Days 2, 4, 6, 8, 11, 15 (Wk 2), 22 (Wk 3), 29 (Wk 4), 43 (Wk 6), 57 (Wk 8), and 85 (Wk 12) during the 12 weeks treatment phase.
Intervention Type
Drug
Intervention Name(s)
Telbivudine
Intervention Description
600 mg monotherapy supplied in film-coated tablets.
Intervention Type
Drug
Intervention Name(s)
Tenofovir
Intervention Description
Tenofovir disoproxil fumarate was supplied in 300 mg tablets
Intervention Type
Drug
Intervention Name(s)
Telbivudine plus tenofovir
Intervention Description
Telbivudine 600 mg and Tenofovir 300 mg were purchased in commercial packs. Patients were instructed to take medication(s) orally every morning either with or without food.
Primary Outcome Measure Information:
Title
Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12.
Description
Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA. Serum HBV DNA determinations were performed at a central laboratory through use of the COBAS TaqMan™ HBV DNA assay (Roche Molecular Systems, Pleasanton, CA, USA) which utilized the Real-time polymerase chain reaction (PCR) method and automated extraction by Cobas Ampliprep (threshold for detection 12 IU/mL). The Screening serum HBV DNA values must be ≥ 7 log10 copies/mL by COBAS TaqMan™ HBV DNA assay.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Weeks 2, 4 and 8.
Description
Baseline HBV DNA is defined as the last pre-dose assessment of HBV DNA. Serum HBV DNA determinations were performed at a central laboratory through use of the COBAS TaqMan™ HBV DNA assay (Roche Molecular Systems, Pleasanton, CA, USA) which utilized the Real-time polymerase chain reaction (PCR) method and automated extraction by Cobas Ampliprep (threshold for detection 12 IU/mL). The Screening serum HBV DNA values must be ≥ 7 log10 copies/mL by COBAS TaqMan™ HBV DNA assay.
Time Frame
Baseline, Week 2, Week 4, Week 8
Title
Percentage of Patients Who Are Polymerase Chain Reaction(PCR)Negative at Week 12
Description
Polymerase Chain Reaction (PCR) Negative is defined as HBV DNA levels <25 copies/ml.
Time Frame
Week 12
Title
Percentage of Patients Who Achieve Hepatitis B "e" Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 12
Description
HBeAg loss is defined as the loss of detectable serum HBeAg in a patient who was HBeAg positive at baseline. HBeAg seroconversion is defined as HBeAg loss with detectable Hepatitis B 'e' antibody (HBeAb). HBeAg stands for hepatitis B "e" antigen. This antigen is a protein from the hepatitis B virus that circulates in infected blood when the virus is actively replicating. The presence of HBeAg suggests that the person is infectious and is able to spread the virus to other people.
Time Frame
Week 12
Title
Characterization of Very Early Viral Kinetics Through Estimated Viral Load
Description
The underlying bi-phasic model of viral kinetics can be described as follows:
V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss
Time Frame
Week 12
Title
Characterization of Very Early Viral Kinetics Through Viral Clearance
Description
The underlying bi-phasic model of viral kinetics can be described as follows:
V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss
Time Frame
Week 12
Title
Characterization of Very Early Viral Kinetics Through Rate of Infected Cell Loss
Description
The underlying bi-phasic model of viral kinetics can be described as follows:
V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss
Time Frame
Week 12
Title
Characterization of Very Early Viral Kinetics Through Efficiency Factor of Blocking Virus Production.
Description
The underlying bi-phasic model of viral kinetics can be described as follows:
V(t) (1 )pI(t) cV(t) I(t) (1 ) (T I(t))V(t) I(t) where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise allinfected and uninfected target cells, and δ the rate of infected cell loss
Time Frame
Week 12
Title
Characterization of Very Early Viral Kinetics Through Half-live of Free Virus
Description
The underlying bi-phasic model of viral kinetics can be described as follows:
V(t) (1 )pI(t) cV(t)I(t) (1 ) (T I(t))V(t) I(t)where V denotes serum viral load, I productively infected cells, ε the efficiency factor of blocking virus production, p the viral production rate, c the viral clearance rate, η the efficiency factor of blocking de novo infection, β the de novo infection rate, Tg comprise all infected and uninfected target cells, and δ the rate of infected cell loss
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Chronic HBV infection, defined as positive serum HBsAg for at least 6 months, or HBsAg positive > 3 months and negative for IgM anti-HBc and positive for IgG anti-HBc
Age < 40 years old
HBeAg positive
HBV DNA > or = to 10^7 copies/mL by Abbott real-time PCR
ALT < or = to 1 ULN
Willing and able to provide written informed consent
No prior oral HBV therapy (e.g., nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)
Is willing and able to comply with the study drug regimen and all other study procedures and requirements
Is willing and able to provide written informed consent before any study assessment is perform
Exclusion Criteria:
Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 × ULN, PT > 1.2 × ULN, platelets < 150,000/mm3, serum albumin < 3.5 g/dL, or prior history of clinical hepatic decompensation (e.g. ascites, jaundice, encephalopathy, variceal hemorrhage).
Received interferon (pegylated or not) therapy within 6 months of the screening visit
α-fetoprotein > 50 ng/mL
Evidence of hepatocellular carcinoma (HCC)
Co-infection with HCV (by serology), or HIV,
Significant renal, cardiovascular, pulmonary, or neurological disease.
Received solid organ or bone marrow transplantation.
Is currently receiving therapy with immunomodulators (e.g., corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion.
Has proximal tubulopathy.
Use of other investigational drugs at the time of enrollment, or within 30 days
History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
Is pregnant or breastfeeding.
Is a women of child-bearing potential (WOCBP)unless post-menopausal or using one or more acceptable method of contraception.
Patient has any other concurrent medical or social condition likely to preclude compliance with the schedule of evaluations in the protocol, or likely to confound the efficacy or safety observations of the study.
Patient is currently abusing alcohol or illicit drugs, or has a history of alcohol abuse or illicit substance abuse within the preceding two years.
Patient has a medical condition that requires prolonged or frequent use of systemic acyclovir or famciclovir.
Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Department of Medicine, Queen Mary Hospital
City
Hong Kong
Country
China
12. IPD Sharing Statement
Learn more about this trial
Effects of Telbivudine and Tenofovir Disoproxil Fumarate Treatment on the Hepatitis B Virus DNA Kinetics in CHB
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