Comparison of Telbivudine Plus Adefovir With Lamivudine Plus Adefovir for the Treatment of Lamivudine-resistant Chronic Hepatitis B at 52 Weeks: A Pilot Study
Information source: Korea University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic Hepatitis B
Intervention: telbivudine plus adefovir (Drug); lamivudine plus adefovir (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Korea University Official(s) and/or principal investigator(s):
Hyung Joon Yim, M.D, Principal Investigator, Affiliation: Korea University
Overall contact:
Hyung Joon Yim, M.D, Phone: 82-31-412-5583, Email: gudwns21@medimail.co.kr
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). 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,
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The mean reduction of serum HBV DNA from the baseline at week 52.
Secondary outcome: HBV DNA undetectability(<20 IU/mL)mean serum HBV DNA level rate of ALT normalization rates of HBeAg loss rate of HBeAg seroconversion at week 52.
Eligibility
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. HBeAg positive or negative chronic hepatitis B patients (positive HBsAg more than 6
months)
2. Age ≥ 18 years old, and ≤70 years old
3. Previous treatment with lamivudine more than 6 months
4. Being on lamivudine at the time of screening
5. Confirmed genotypic resistance to lamivudine by RFMP (rtM204V or I)
6. Presence of virologic breakthrough ≥1 log increase of HBV DNA above na dir)
7. HBV DNA ≥ 20,000 IU/mL
8. 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:
1. Out of inclusion criteria
2. Presence of adefovir resistance (rtA181T or V, rtN236T) by RFMP assay
3. 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
4. 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.
5. History of treatment with nucleos(t)ide analogues other than lamivudine more than 4
weeks
6. History of immune modulatory drugs (interferon, thymosin-alfa) within 24 weeks of
screening
7. Liver transplant patient
8. Patient co-infected with HIV, HCV, or HDV
9. Patient with metabolic or genetic liver disease that may affect serum ALT level
10. Habitual alcohol consumption (>140 g/week for male, >70 g/week for female)
11. 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,)
12. Pregnant or lactating woman
13. Menstruating woman unwilling to use appropriate methods of contraception (ie. Condom,
oral contraceptives, tubal ligation)
14. Patient with hepatocellular carcinoma (treated or not treated)
15. Patient with any untreated malignancy
16. Patient with history of malignancy cured within 5 years of screening
Locations and Contacts
Hyung Joon Yim, M.D, Phone: 82-31-412-5583, Email: gudwns21@medimail.co.kr
Korea University Ansan Hospital, Ansan, Gyeonggi-do 425-707, Korea, Republic of; Recruiting
Hyung Joon Yim, M.D, Phone: 82-31-412-5583, Email: gudwns21@medimail.co.kr
Additional Information
Starting date: May 2011
Last updated: March 3, 2013
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