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Entecavir in Lamivduine Experienced Patients
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A Randomized, Placebo-Controlled Study (ETV-056) in China of the Efficacy and safety of Entecavir in Chronic Hepatitis B Patients Who have Failed Lamivudine"
About 400 million people worldwide are chronically infected with hepatitis B (HBV) virus; 67% live in the Asia-Pacific region. Prolonged treatment with lamivudine is frequently associated with development of mutations in the HBV polymerase gene conferring resistance to lamivudine. The emergence of lamivudine resistance may result in breakthrough viremia, ALT elevation & progression of disease. The objective of this study is to evaluate the treatment with entecavir 1.0 mg daily versus placebo for 12 weeks in Chinese patients who have failed lamivudine.
Guangbi Yao reported study results at AASLD. This study was double-blind, placebo-controlled & conducted at 5 centers in China. Eligible patients had chronic HBV and documented LAM failure, had discontinued LAM therapy at least 12 weeks prior to enrollment, had HBV DNA >=105 copies/mL by PCR assay & ALT levels not exceeding 10 x ULN. In the double-blind phase of the study, patients were randomized (4:1) to receive ETV 1.0 mg QD (n=116) or placebo (n=29) for 12 weeks. In the subsequent open-label phase, all patients received ETV 1.0 mg for up to 36 weeks. The primary endpoint was the mean change from baseline at week 12 in HBV DNA by PCR assay.
75% of patients were male, the mean age was 35 yrs, 90% were HBeAg-positive, 41% had ALT >=1.25 x ULN, but only 42% had LAM resistant virus detected by HBV DNA polymerase sequence analysis at baseline.
The mean baseline HBV DNA level by PCR assay was 8.79 log copies/ml. The mean change in HBV DNA levels at week 12 was -4.30 log copies/mL for the ETV group vs -0.15 for the placebo group.
Entecavir was also superior to placebo for the proportion of patients with HBV DNA levels <0.7 MEq/mL by bDNA assay at week 12 (74% vs 10%).
Among patients with abnormal ALT levels at baseline, 71% of patients treated with ETV had normalized ALT at week 12 compared to 7% receiving placebo. After only 12 weeks of treatment, 8% of patients receiving ETV achieved HBV DNA <400 copies/mL by PCR compared to no patients in the placebo group.
A rapid reduction in HBV DNA was observed in patients receiving ETV. By week 2, patients receiving ETV had -2.65 log copies/ml HBV DNA reduction compared to 0.06 for placebo.
The overall incidence of adverse events was similar between treatment groups: 33% for ETV & 28% for placebo. There were no grade ¾ adverse events, serious adverse events, or discontinuations due to AE among patients treated with ETV.
ALT flares (ALT >2 x baseline & >10 x ULN) occurred in 2 patients in the ETV group (2%) and 3 in the placebo group (10%). ALT flares in ETV patients were self-limiting and both patients had achieved HBV DNA <0.7 MEq/ml by bDNA by week 12.
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