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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-nave 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

Page last updated: August 23, 2015

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