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A Randomized Trial of Telbivudine (LdT) vs. Adefovir for HBeAg-Positive Chronic Hepatitis B: Results of the Primary Week 24 Analysis
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Reported by Jules Levin
EASL Annual Meeting, 26-30 April 2006, Vienna
HL-Y. Chan, C-L Lai, M Cho, J Heathcote, Y-M Moon, Y-C Chao, R Myers, G Minuk, P Marcellin, L Jeffers, W Sievert, R Kaiser, G Chao, G Harb, N Brown, and the 018 Study Group
BACKGROUND
Telbivudine (L-deoxythymidine; LdT) is a specific inhibitor of HBV polymerase, with a favorable preclinical and clinical safety profile.
Telbivudine showed significantly greater efficacy compared with lamivudine in an international phase III trial (GLOBE):
-- Log10 suppression of HBV DNA
-- HBV DNA clearance to PCR non-delectability
-- Histologic improvement
-- Less resistance (8% vs 2-3%)
Today, we present the initial results of a clinical trial comparing the safety and antiviral efficacy of telbivudine and adefovir dipivoxil in HBeAg positive patients with chronic hepatitis B.
Author Summary: Efficacy of Telbivudine at 24 Weeks
Significantly greater and more rapid viral suppression with telbivudine:
-- Log10 HBV DNA reduction at 24 weeks: 6.30 vs. 4.97 log10 for adefovir
-- Significantly greater viral suppression with telbivudine by week 2 (p=0.008)
-- PCR non-detectable at Week 24: 39%, vs. 12% for adefovir
Potentially greater HBeAg loss with telbivudine:
-- 16%, vs. 10% for adefovir at Week 24
Significantly less primary treatment failure with telbivudine:
-- 42% of adefovir recipients failed to achieve viral load below
5 log10 within 6 months, vs. 5% for telbivudine (p<0.001)
Both treatments well tolerated
Study Design
018 Trial: Telbivudine vs. Adefovir in HBeAg+ Chronic Hepatitis B Patients
Randomized, open label, multicenter trial
-- Enrolled ITT population: 135 patients
Key entry criteria:
-- Chronic hepatitis B with compensated liver disease
-- HBeAg positive, treatment-naive
Serum HBV DNA >106 by COBAS Amplicor PCR assay; ALT 1.3-10 xULN
Baseline randomization: 1:1:1
Endpoints
018 Trial: Telbivudine vs. Adefovir in HBeAg+ Chronic Hepatitis B Patients
Primary efficacy endpoint:
Serum HBV DNA reduction at Week 24
Key secondary efficacy endpoints:
- Clearance of HBV DNA to PCR-nondetectable
- ALT normalization
- HBeAg loss
Treatment failure and resistance:
- Primary treatment failure: serum HBV DNA never below 5 log10
- Resistance: viral breakthrough with resistance mutations confirmed by gene sequencing
Baseline Demographic & Disease Parameters
018 Trial: Telbivudine vs. Adefovir in HBeAg+ Chronic Hepatitis B Patients
One grade 3/4 laboratory abnormality: neutropenia, in a patient receiving telbivudine - resolved by next visit 6 days later, with continued treatment
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