Chronic Viral Hepatitis B Without Delta-agentPhase 3TERESANCT01595685
Telbivudine Versus Entecavir in Reducing Serum HBsAg Levels in Patients With HBeAg-positive Chronic Hepatitis B
A Phase 3 study testing Telbivudine and Entecavir in people with Chronic Viral Hepatitis B Without Delta-agent, run by Asan Medical Center at 1 site in South Korea.
Trial summary
The goal of chronic hepatitis B (CHB) treatment is complete and permanent eradication of hepatitis B virus (HBV) from patient's body, which is best represented by serum HBsAg loss accompanied by undetectable serum HBV DNA level. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Viral Hepatitis B Without Delta-agent
- What is being tested?
- Telbivudine and Entecavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 1 siteSouth Korea
- Study dates
- May 2012to Dec 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HBsAg titer > 1,000 IU/mL
- HBeAg positive at study entry and at the baseline of ETV treatment
- HBV DNA undetectable (<15 IU/mL) at least 2 occasions of more than 3 months apart
- Treatment with entecavir (0.5 mg/day) for more than 1 year
- Patient is ambulatory.
- Patient is able and willing to give informed consent.
Who cannot join
- Prior exposure to oral nucloes(t)ide analogue other than entecavir
- Prior any exposure to interferon or pegylated interferon
- Cirrhosis with Child-Pugh score ≥8
- Hepatocellular carcinoma Identified or suspected
- Other malignancy
- Prior organ transplantation
Show all 9Show fewer
- Under immunosuppressive agent
- Renal insufficiency (serum creatinine > 1.4)
- Pregnant woman or willing to be pregnant woman or man
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Open-label Trial Comparing Telbivudine vs, Entecavir in Reducing Serum HBsAg Levels in Patients With HBeAg-positive Chronic Hepatitis B Who Have Achieved Serum HBV DNA Undetectability by Preceding Entecavir Treatment
The goal of chronic hepatitis B (CHB) treatment is complete and permanent eradication of hepatitis B virus (HBV) from patient's body, which is best represented by serum HBsAg loss accompanied by undetectable serum HBV DNA level.
While the most recently approved nucleos(t)ide analogues (NA) have marked antiviral potency and can induce HBV DNA undetectability in the majority of patients through prolonged treatment, NA need to be given long term, almost indefinitely, in most cases because they suppress HBV DNA only during therapy. For example, even after HBeAg-loss by a potent NA, suppression of serum HBV DNA to undetectable level is sustained only in about 23%-37% at 24 weeks off treatment. Thus, continuous therapy with NA until HBsAg clearance remains necessary in a majority of cases.
Read more
The recent availability of commercial quantitative assays of serum hepatitis B surface antigen (HBsAg) has enabled quantitative HBsAg to be used as a biomarker for prognosis and treatment response in CHB. It has been suggested that HBsAg decline during lamivudine or entecavir therapy is slower and less pronounced compared to interferon treatment, despite a higher effect on HBV DNA suppression. Based on HBsAg kinetics, it has been estimated that the predicted median time to HBsAg loss in patients treated with lamivudine or entecavir is more than 30 years. Thus, treatment that can induce rapid decline of HBsAg would have clear advantage in reducing the treatment duration required to achieve HBsAg-loss.
Interestingly, in a recent preliminary study, 24-weeks of treatment with telbivudine has induced HBsAg decline as comparable to pegylated interferon treatment. Although there has been no head-to-head trial comparing NAs in inducing HBsAg decline, previous studies consistently suggested that the decline of HBsAg is greater during telbivudine treatment compared with lamivudine or entecavir.
Thus, in this clinical trial, the investigators will investigate whether telbivudine is more effective in inducing HBsAg decline compared with entecavir in HBeAg-positive CHB patients who have achieved undetectable serum HBV DNA by preceding entecavir treatment.
Read the detailed description
A single-center randomized active-controlled open-label superiority trial
- Patients will be randomly assigned 1:1 to receive telbivudine (600 mg/day) or ongoing entecavir (0.5 mg/day) for 48 weeks.
- Eligible patients will be randomized using blocks of permuted treatment assignments after stratification by HBsAg level (1,000 IU/mL-5,000 IU/mL and ≥5,000 IU/mL IU/mL) and by entecavir treatment duration (1 year-2 year, ≥2 year).
- Because over 98% of Korean patients with CHB have HBV genotype C,9 HBV genotype will not determined or be regarded as a stratification factor.
- There will be no interruption in entecavir therapy before randomization.
- Patients' treatment information will be retrospectively collected during entecavir treatment phase as well (DNA change, HBeAg status, HBsAg titre, ALT, and treatment duration. etc)
- Patients will be screened within 4 weeks before randomization to determine study eligibility.
- Being tested
- Telbivudine, Entecavir
- Keywords
- HBeAg-positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TelbivudineDrug
Also called Sebivo
Telbivudine 600 mg Daily Oral
EntecavirDrug
Also called Baraclude
Entecavir 0.5 mg Daily Oral
| Study group | Role | What they receive |
|---|---|---|
| Telbivudine | Experimental | Telbivudine 600 mg Daily Oral Receives: Drug: Telbivudine |
| Entecavir | Active comparator | Entecavir 0.5 mg Daily Oral Receives: Drug: Entecavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
HBsAg titer at 48 weeks
Measured: at 48 weeks
Secondary outcomes (7)
Proportion of patients with serum HBsAg decline of ≥0.5 log10 IU/mL and <1.0 log10 IU/mL
Measured: at 48 weeks of treatment
Proportion of patients with serum HBsAg decline greater than 1.0 log10 IU/mL
Measured: at 48 weeks of treatment
Proportion of patients with serum HBsAg loss
Measured: at 48 weeks of treatment
Proportion of patients with serum HBeAg loss or HBeAg seroconversion
Measured: at 48 weeks of treatment
Proportion of patients with virologic rebound or genotypic resistance
Measured: up to 48 weeks of treatment
Proportion of patients with normal ALT
Measured: at 48 weeks of treatment
Adverse events: Creatine kinase level, GFR, Muscle events, Other AEs
Measured: up to 48 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2012 (estimated)
- Study startMay 2012
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Viral Hepatitis B Without Delta-agentStudies of the same condition, open and under way.
- More trials run by Asan Medical CenterThe 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
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Young-Suk Lim, Asan Medical Center
- Investigators
- Young-Suk Lim, M.D., Ph.D., Principal investigator, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01595685
- Sponsor's protocol ID
- AMC2012-0201
- Acronym
- TERESA
- Status last verified
- Jan 2017
- First submitted
- 8 May 2012
- Last updated
- 26 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
An J, Lim YS, Kim GA, Han SB, Jeong W, Lee D, Shim JH, Lee HC, Lee YS. Telbivudine versus entecavir in patients with undetectable hepatitis B virus DNA: a randomized trial. BMC Gastroenterol. 2017 Jan 19;17(1):15. doi: 10.1186/s12876-017-0572-2.
PubMed 28103819
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label Trial Comparing Telbivudine vs, Entecavir in Reducing Serum HBsAg Levels in Patients With HBeAg-positive Chronic Hepatitis B Who Have Achieved Serum HBV DNA Undetectability by Preceding Entecavir Treatment
- ClinicalTrials.gov ID
- NCT01595685
- Acronym / sponsor ID
- TERESA / AMC2012-0201
- Keywords
- HBeAg-positive
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Study start
- May 2012
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 10 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of chronic hepatitis B (CHB) treatment is complete and permanent eradication of hepatitis B virus (HBV) from patient's body, which is best represented by serum HBsAg loss accompanied by undetectable serum HBV DNA level.
While the most recently approved nucleos(t)ide analogues (NA) have marked antiviral potency and can induce HBV DNA undetectability in the majority of patients through prolonged treatment, NA need to be given long term, almost indefinitely, in most cases because they suppress HBV DNA only during therapy. For example, even after HBeAg-loss by a potent NA, suppression of serum HBV DNA to undetectable level is sustained only in about 23%-37% at 24 weeks off treatment. Thus, continuous therapy with NA until HBsAg clearance remains necessary in a majority of cases.
The recent availability of commercial quantitative assays of serum hepatitis B surface antigen (HBsAg) has enabled quantitative HBsAg to be used as a biomarker for prognosis and treatment response in CHB. It has been suggested that HBsAg decline during lamivudine or entecavir therapy is slower and less pronounced compared to interferon treatment, despite a higher effect on HBV DNA suppression. Based on HBsAg kinetics, it has been estimated that the predicted median time to HBsAg loss in patients treated with lamivudine or entecavir is more than 30 years. Thus, treatment that can induce rapid decline of HBsAg would have clear advantage in reducing the treatment duration required to achieve HBsAg-loss.
Interestingly, in a recent preliminary study, 24-weeks of treatment with telbivudine has induced HBsAg decline as comparable to pegylated interferon treatment. Although there has been no head-to-head trial comparing NAs in inducing HBsAg decline, previous studies consistently suggested that the decline of HBsAg is greater during telbivudine treatment compared with lamivudine or entecavir.
Thus, in this clinical trial, the investigators will investigate whether telbivudine is more effective in inducing HBsAg decline compared with entecavir in HBeAg-positive CHB patients who have achieved undetectable serum HBV DNA by preceding entecavir treatment.
Detailed description
A single-center randomized active-controlled open-label superiority trial
- Patients will be randomly assigned 1:1 to receive telbivudine (600 mg/day) or ongoing entecavir (0.5 mg/day) for 48 weeks.
- Eligible patients will be randomized using blocks of permuted treatment assignments after stratification by HBsAg level (1,000 IU/mL-5,000 IU/mL and ≥5,000 IU/mL IU/mL) and by entecavir treatment duration (1 year-2 year, ≥2 year).
- Because over 98% of Korean patients with CHB have HBV genotype C,9 HBV genotype will not determined or be regarded as a stratification factor.
- There will be no interruption in entecavir therapy before randomization.
- Patients' treatment information will be retrospectively collected during entecavir treatment phase as well (DNA change, HBeAg status, HBsAg titre, ALT, and treatment duration. etc)
- Patients will be screened within 4 weeks before randomization to determine study eligibility.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Telbivudine | Experimental | Drug: TelbivudineTelbivudine 600 mg Daily Oral |
| Entecavir | Active comparator | Drug: EntecavirEntecavir 0.5 mg Daily Oral |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- HBsAg titer > 1,000 IU/mL
- HBeAg positive at study entry and at the baseline of ETV treatment
- HBV DNA undetectable (<15 IU/mL) at least 2 occasions of more than 3 months apart
- Treatment with entecavir (0.5 mg/day) for more than 1 year
- Patient is ambulatory.
Key exclusion criteria (9 listed)
- Prior exposure to oral nucloes(t)ide analogue other than entecavir
- Prior any exposure to interferon or pegylated interferon
- Cirrhosis with Child-Pugh score ≥8
- Hepatocellular carcinoma Identified or suspected
- Other malignancy
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 |
|---|---|---|
| TelbivudineAlso: SebivoTelbivudine 600 mg Daily Oral | Drug | Telbivudine |
| EntecavirAlso: BaracludeEntecavir 0.5 mg Daily Oral | Drug | Entecavir |
Primary outcome
HBsAg titer at 48 weeks
Time frame: at 48 weeks
7 secondary outcomes
Proportion of patients with serum HBsAg decline of ≥0.5 log10 IU/mL and <1.0 log10 IU/mL
Time frame: at 48 weeks of treatment
Proportion of patients with serum HBsAg decline greater than 1.0 log10 IU/mL
Time frame: at 48 weeks of treatment
Proportion of patients with serum HBsAg loss
Time frame: at 48 weeks of treatment
Proportion of patients with serum HBeAg loss or HBeAg seroconversion
Time frame: at 48 weeks of treatment
Proportion of patients with virologic rebound or genotypic resistance
Time frame: up to 48 weeks of treatment
Proportion of patients with normal ALT
Time frame: at 48 weeks of treatment
Adverse events: Creatine kinase level, GFR, Muscle events, Other AEs
Time frame: up to 48 weeks of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2017.
- Derived from this study: PubMed 28103819An J, Lim YS, Kim GA, Han SB, Jeong W, Lee D, Shim JH, Lee HC, Lee YS. Telbivudine versus entecavir in patients with undetectable hepatitis B virus DNA: a randomized trial. BMC Gastroenterol. 2017 Jan 19;17(1):15. doi: 10.1186/s12876-017-0572-2.
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.
Young-Suk Lim, M.D., Ph.D. principal investigator
Asan Medical Center
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 and Entecavir in people with Chronic Viral Hepatitis B Without Delta-agent, run by Asan Medical Center at 1 site in South Korea.
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 6 inclusion and 9 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 26 Jan 2017. 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 South Korea. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
HBsAg titer at 48 weeks (time frame: at 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01595685, which also lists 1 linked publication.
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 26 Jan 2017.