- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01804387
Comparison of Telbivudine Plus Adefovir With Lamivudine Plus Adefovir for the Treatment of Lamivudine-resistant Chronic Hepatitis B at 52 Weeks: A Pilot Study (TeSLA)
March 3, 2013 updated by: Hyung Joon Yim, Korea University
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 Overview
Status
Unknown
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
60
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Hyung Joon Yim, M.D
- Phone Number: 82-31-412-5583
- Email: gudwns21@medimail.co.kr
Study Locations
-
-
Gyeonggi-do
-
Ansan, Gyeonggi-do, Korea, Republic of, 425-707
- Recruiting
- Korea University Ansan Hospital
-
Contact:
- Hyung Joon Yim, M.D
- Phone Number: 82-31-412-5583
- Email: gudwns21@medimail.co.kr
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Telbivudine plus adefovir
study drugs
|
telbivudine 600 mg qd plus adefovir 10 mg qd
Other Names:
|
Active Comparator: Lamivudine plus adefovir
standard drugs
|
lamivudine 100 mg qd plus adefovir 10mg qd
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The mean reduction of serum HBV DNA from the baseline at week 52.
Time Frame: up to the end of year 1 (52 weeks)
|
up to the end of year 1 (52 weeks)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HBV DNA undetectability(<20 IU/mL)
Time Frame: up to the end of year 1 (52 weeks)
|
At the end of year 1 in the two groups, HBV DNA undetectability by real time PCR will be assessed.
|
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)
|
up to the end of year 1 (52 weeks)
|
|
rate of ALT normalization
Time Frame: up to the end of year 1 (52 weeks)
|
up to the end of year 1 (52 weeks)
|
|
rates of HBeAg loss
Time Frame: up to the end of year 1 (52 weeks)
|
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)
|
up to the end of year 1 (52 weeks)
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Antiviral resistance rate
Time Frame: up to the end of year 1 (52 weeks)
|
up to the end of year 1 (52 weeks)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Hyung Joon Yim, M.D, Korea University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2011
Primary Completion (Anticipated)
December 1, 2013
Study Completion (Anticipated)
May 1, 2014
Study Registration Dates
First Submitted
December 23, 2011
First Submitted That Met QC Criteria
March 3, 2013
First Posted (Estimate)
March 5, 2013
Study Record Updates
Last Update Posted (Estimate)
March 5, 2013
Last Update Submitted That Met QC Criteria
March 3, 2013
Last Verified
March 1, 2013
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Hepatitis, Chronic
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Lamivudine
- Telbivudine
- Adefovir
- Adefovir dipivoxil
Other Study ID Numbers
- TeSLA study
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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