Hepatitis B VirusPhase 3NCT00805675
Effects of Telbivudine and Tenofovir Disoproxil Fumarate Treatment on the Hepatitis B Virus DNA Kinetics in CHB
A Phase 3 study testing Telbivudine, Tenofovir and Telbivudine plus tenofovir in people with Hepatitis B Virus, run by Novartis Pharmaceuticals at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Hepatitis B Virus
- What is being tested?
- Telbivudine, Tenofovir and Telbivudine plus tenofovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 1 siteChina
- Study dates
- Nov 2008to Dec 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Hepatitis B Virus
- Being tested
- Telbivudine, Tenofovir, Telbivudine plus tenofovir
- Keywords
- Chronic HBV, Asian adult subjects with chronic HBV, in immune tolerant phase, and positive for hepatitis B e antigen (HBeAg)
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TelbivudineDrug
600 mg monotherapy supplied in film-coated tablets.
TenofovirDrug
Tenofovir disoproxil fumarate was supplied in 300 mg tablets
Telbivudine plus tenofovirDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Telbivudine 600 mg monotherapy | Experimental | 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. Receives: Drug: Telbivudine |
| Tenofovir disproxil fumarate 300 mg monotherapy | Active comparator | 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. Receives: Drug: Tenofovir |
| Telbivudine 600 mg and Tenofovir 300 mg | Active comparator | 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. Receives: Drug: Telbivudine plus tenofovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 12
Secondary outcomes (8)
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.
Measured: Baseline, Week 2, Week 4, Week 8
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.
Measured: Week 12
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.
Measured: Week 12
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
Measured: Week 12
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
Measured: Week 12
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
Measured: Week 12
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
Measured: Week 12
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
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2008 (estimated)
- Study startNov 2008
- Primary completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatitis B VirusStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00805675
- Sponsor's protocol ID
- CLDT600AHK01
- Status last verified
- Jan 2012
- First submitted
- 9 Dec 2008
- Last updated
- 28 Feb 2012
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00805675
- Acronym / sponsor ID
- CLDT600AHK01
- Conditions
- Hepatitis B Virus
- Keywords
- Chronic HBV, Asian adult subjects with chronic HBV, in immune tolerant phase, and positive for hepatitis B e antigen (HBeAg)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2008
- Primary completion
- Dec 2010 (actual)
- First posted
- 10 Dec 2008 (estimated)
- Results
- Posted 28 Feb 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Telbivudine 600 mg monotherapy | Experimental | Drug: TelbivudineAll 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. |
| Tenofovir disproxil fumarate 300 mg monotherapy | Active comparator | Drug: TenofovirAll 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. |
| Telbivudine 600 mg and Tenofovir 300 mg | Active comparator | Drug: Telbivudine plus tenofovirAll 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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (17 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Telbivudine600 mg monotherapy supplied in film-coated tablets. | Drug | Telbivudine 600 mg monotherapy |
| TenofovirTenofovir disoproxil fumarate was supplied in 300 mg tablets | Drug | Tenofovir disproxil fumarate 300 mg monotherapy |
| Telbivudine plus tenofovirTelbivudine 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. | Drug | Telbivudine 600 mg and Tenofovir 300 mg |
Primary outcome
Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12.
Time frame: Baseline, 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.
8 secondary outcomes
Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Weeks 2, 4 and 8.
Time frame: Baseline, Week 2, Week 4, Week 8
Percentage of Patients Who Are Polymerase Chain Reaction(PCR)Negative at Week 12
Time frame: Week 12
Percentage of Patients Who Achieve Hepatitis B "e" Antigen (HBeAg) Loss and HBeAg Seroconversion at Week 12
Time frame: Week 12
Characterization of Very Early Viral Kinetics Through Estimated Viral Load
Time frame: Week 12
Characterization of Very Early Viral Kinetics Through Viral Clearance
Time frame: Week 12
Characterization of Very Early Viral Kinetics Through Rate of Infected Cell Loss
Time frame: Week 12
Characterization of Very Early Viral Kinetics Through Efficiency Factor of Blocking Virus Production.
Time frame: Week 12
Characterization of Very Early Viral Kinetics Through Half-live of Free Virus
Time frame: Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Telbivudine, Tenofovir and Telbivudine plus tenofovir in people with Hepatitis B Virus, run by Novartis Pharmaceuticals at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Feb 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Level From Baseline to Week 12. (time frame: Baseline, Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2012.