Chronic Hepatitis BPhase 4TeSLANCT01804387
Comparison of Telbivudine Plus Adefovir With Lamivudine Plus Adefovir for the Treatment of Lamivudine-resistant Chronic Hepatitis B at 52 Weeks: A Pilot Study
A Phase 4 study testing telbivudine plus adefovir and lamivudine plus adefovir in people with Chronic Hepatitis B, run by Korea University at 1 site in South Korea.
Trial summary
Lamivudine had been widely used for treatment-naïve chronic hepatitis B patients. However, development of antiviral resistance has been known as the major drawback: Incidence of lamivudine resistance was reported to be approximately 70% after 5 years (Lok AS et al, 2003). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- telbivudine plus adefovir and lamivudine plus adefovir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteSouth Korea
- Study dates
- May 2011to May 2014
- Phase
- Phase 4
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HBeAg positive or negative chronic hepatitis B patients (positive HBsAg more than 6 months)
- Age ≥ 18 years old, and ≤70 years old
- Previous treatment with lamivudine more than 6 months
- Being on lamivudine at the time of screening
- Confirmed genotypic resistance to lamivudine by RFMP (rtM204V or I)
- Presence of virologic breakthrough ≥1 log increase of HBV DNA above na dir)
- HBV DNA ≥ 20,000 IU/mL
- Patient willing to give an informed consent (If patient is <20 years old, the parent or legal guardian also need to give an informed consent)
Who cannot join
- Out of inclusion criteria
- Presence of adefovir resistance (rtA181T or V, rtN236T) by RFMP assay
- Laboratory abnormalities as follows at screening: AFP>100 ng/mL, serum phosphorous level<2.4 mg/dL, serum creatinine level> 1.5 mg/dL or creatinine clearance < 50 mL/min
- Patient with a history of decompensated liver disease: Any patients with a history of ascites, hepatic encephalopathy, variceal bleeding, jaundice, or CTP>7 points should be excluded.
- History of treatment with nucleos(t)ide analogues other than lamivudine more than 4 weeks
- History of immune modulatory drugs (interferon, thymosin-alfa) within 24 weeks of screening
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- Liver transplant patient
- Patient co-infected with HIV, HCV, or HDV
- Patient with metabolic or genetic liver disease that may affect serum ALT level
- Habitual alcohol consumption (>140 g/week for male, >70 g/week for female)
- Patient not able to stop drugs that may affect ALT or HBV DNA level during study periods (ie. Steroid, immune-suppressants, non-steroidal anti-inflammatory drugs, acetaminophen,)
- Pregnant or lactating woman
- Menstruating woman unwilling to use appropriate methods of contraception (ie. Condom, oral contraceptives, tubal ligation)
- Patient with hepatocellular carcinoma (treated or not treated)
- Patient with any untreated malignancy
- Patient with history of malignancy cured within 5 years of screening
Trial locations and contacts
1 site in 1 country.
South Korea1 site, 1 recruiting
- Recruiting
Korea University Ansan Hospital
Ansan, Gyeonggi-do, 425-707
Hyung Joon Yim, M.D, 82-31-412-5583, gudwns21@medimail.co.kr
About this study
Lamivudine had been widely used for treatment-naïve chronic hepatitis B patients. However, development of antiviral resistance has been known as the major drawback: Incidence of lamivudine resistance was reported to be approximately 70% after 5 years (Lok AS et al, 2003). For the treatment of lamivudine resistance, adefovir has been widely used (Lok AS and McMahon B, 2009). However, switching to adefovir monotherapy was also reported to be at high risk of resistance, 25% at year 2 (Yeon JE et al, 2006). Recently, adding adefovir on lamivudine was shown to be superior to switching to adefovir monotherapy by decreasing the adefovir resistance (Rapti I et al, 2007, Lampertico P et al, 2007). However, combination of adefovir and lamivudine does not increase antiviral activity compared with adefovir monotherapy in patients with lamivudine resistance (Peters MG et al, 2004). As many patients are still viremic with the treatment of lamivudine and adefovir over 1 year, the investigators need more potent combination of the drugs. Telbivudine is a new nucleoside analogue with potent antiviral activity. The previous phase III study has shown the superiority of telbivudine over lamivudine in HBeAg positive and negative subjects (Lai CL et al, 2007). Therefore, telbivudine plus adefovir may be a better treatment option than lamivudine plus adefovir for the lamivudine-resistant chronic hepatitis B patients. No study assessing the efficacy of telbivudine plus adefovir has been conducted for these patients. The aim of this study is to evaluate the safety and efficacy of telbivudine plus adefovir compared with lamivudine plus adefovir in lamivudine resistant chronic hepatitis B patients at the end of 1 year follow-up,
- Conditions
- Chronic Hepatitis B
- Being tested
- telbivudine plus adefovir, lamivudine plus adefovir
- Keywords
- Chronic Hepatitis B, Telbivudine, Adefovir, Lamivudine resistance
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
telbivudine plus adefovirDrug
Also called telbivudine (sevibo), adefovir (hepsera)
telbivudine 600 mg qd plus adefovir 10 mg qd
lamivudine plus adefovirDrug
Also called lamivudine (zeffix), adefovir (hepsera)
lamivudine 100 mg qd plus adefovir 10mg qd
| Study group | Role | What they receive |
|---|---|---|
| Telbivudine plus adefovir | Active comparator | study drugs Receives: Drug: telbivudine plus adefovir |
| Lamivudine plus adefovir | Active comparator | standard drugs Receives: Drug: lamivudine plus adefovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
The mean reduction of serum HBV DNA from the baseline at week 52.
Measured: up to the end of year 1 (52 weeks)
Secondary outcomes (5)
HBV DNA undetectability(<20 IU/mL)
At the end of year 1 in the two groups, HBV DNA undetectability by real time PCR will be assessed.
Measured: up to the end of year 1 (52 weeks)
mean serum HBV DNA level
Measured: up to the end of year 1 (52 weeks)
rate of ALT normalization
Measured: up to the end of year 1 (52 weeks)
rates of HBeAg loss
Measured: up to the end of year 1 (52 weeks)
rate of HBeAg seroconversion at week 52.
Measured: up to the end of year 1 (52 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2013 (estimated)
- Study startMay 2011
- Primary completionDec 2013 (estimated)
- Study completionMay 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Korea University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hyung Joon Yim, Korea University
- Investigators
- Hyung Joon Yim, M.D, Principal investigator, Korea University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01804387
- Sponsor's protocol ID
- TeSLA study
- Acronym
- TeSLA
- Status last verified
- Mar 2013
- First submitted
- 23 Dec 2011
- Last updated
- 5 Mar 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Telbivudine Plus Adefovir With Lamivudine Plus Adefovir for the Treatment of Lamivudine-resistant Chronic Hepatitis B at 52 Weeks: A Pilot Study
- ClinicalTrials.gov ID
- NCT01804387
- Acronym / sponsor ID
- TeSLA / TeSLA study
- Conditions
- Chronic Hepatitis B
- Keywords
- Chronic Hepatitis B, Telbivudine, Adefovir, Lamivudine resistance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Korea UniversityUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Dec 2013 (estimated)
- Study completion
- May 2014 (estimated)
- First posted
- 5 Mar 2013 (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.
Lamivudine had been widely used for treatment-naïve chronic hepatitis B patients. However, development of antiviral resistance has been known as the major drawback: Incidence of lamivudine resistance was reported to be approximately 70% after 5 years (Lok AS et al, 2003). For the treatment of lamivudine resistance, adefovir has been widely used (Lok AS and McMahon B, 2009). However, switching to adefovir monotherapy was also reported to be at high risk of resistance, 25% at year 2 (Yeon JE et al, 2006). Recently, adding adefovir on lamivudine was shown to be superior to switching to adefovir monotherapy by decreasing the adefovir resistance (Rapti I et al, 2007, Lampertico P et al, 2007). However, combination of adefovir and lamivudine does not increase antiviral activity compared with adefovir monotherapy in patients with lamivudine resistance (Peters MG et al, 2004). As many patients are still viremic with the treatment of lamivudine and adefovir over 1 year, the investigators need more potent combination of the drugs. Telbivudine is a new nucleoside analogue with potent antiviral activity. The previous phase III study has shown the superiority of telbivudine over lamivudine in HBeAg positive and negative subjects (Lai CL et al, 2007). Therefore, telbivudine plus adefovir may be a better treatment option than lamivudine plus adefovir for the lamivudine-resistant chronic hepatitis B patients. No study assessing the efficacy of telbivudine plus adefovir has been conducted for these patients. The aim of this study is to evaluate the safety and efficacy of telbivudine plus adefovir compared with lamivudine plus adefovir in lamivudine resistant chronic hepatitis B patients at the end of 1 year follow-up,
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Telbivudine plus adefovir | Active comparator | Drug: telbivudine plus adefovirstudy drugs |
| Lamivudine plus adefovir | Active comparator | Drug: lamivudine plus adefovirstandard drugs |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- HBeAg positive or negative chronic hepatitis B patients (positive HBsAg more than 6 months)
- Age ≥ 18 years old, and ≤70 years old
- Previous treatment with lamivudine more than 6 months
- Being on lamivudine at the time of screening
- Confirmed genotypic resistance to lamivudine by RFMP (rtM204V or I)
Key exclusion criteria (16 listed)
- Out of inclusion criteria
- Presence of adefovir resistance (rtA181T or V, rtN236T) by RFMP assay
- Laboratory abnormalities as follows at screening: AFP>100 ng/mL, serum phosphorous level<2.4 mg/dL, serum creatinine level> 1.5 mg/dL or creatinine clearance < 50 mL/min
- Patient with a history of decompensated liver disease: Any patients with a history of ascites, hepatic encephalopathy, variceal bleeding, jaundice, or CTP>7 points should be excluded.
- History of treatment with nucleos(t)ide analogues other than lamivudine more than 4 weeks
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 |
|---|---|---|
| telbivudine plus adefovirAlso: telbivudine (sevibo), adefovir (hepsera)telbivudine 600 mg qd plus adefovir 10 mg qd | Drug | Telbivudine plus adefovir |
| lamivudine plus adefovirAlso: lamivudine (zeffix), adefovir (hepsera)lamivudine 100 mg qd plus adefovir 10mg qd | Drug | Lamivudine plus adefovir |
Primary outcome
The mean reduction of serum HBV DNA from the baseline at week 52.
Time frame: up to the end of year 1 (52 weeks)
5 secondary outcomes
HBV DNA undetectability(<20 IU/mL)
Time frame: up to the end of year 1 (52 weeks)
mean serum HBV DNA level
Time frame: up to the end of year 1 (52 weeks)
rate of ALT normalization
Time frame: up to the end of year 1 (52 weeks)
rates of HBeAg loss
Time frame: up to the end of year 1 (52 weeks)
rate of HBeAg seroconversion at week 52.
Time frame: up to the end of year 1 (52 weeks)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2013.
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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.
Hyung Joon Yim, M.D principal investigator
Korea University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing telbivudine plus adefovir and lamivudine plus adefovir in people with Chronic Hepatitis B, run by Korea University 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 8 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 5 Mar 2013. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hyung Joon Yim, M.D (82-31-412-5583, gudwns21@medimail.co.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The mean reduction of serum HBV DNA from the baseline at week 52. (time frame: up to the end of year 1 (52 weeks)). 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 5 Mar 2013.