Twenty-four-week clevudine therapy showed potent and sustained antiviral activity in HBeAg-positive chronic hepatitis B.
Clevudine is a pyrimidine analogue with potent and sustained antiviral activity against HBV. The present study evaluated the safety and efficacy of 30 mg clevudine once daily for 24 weeks and assessed the durable antiviral response for 24 weeks after cessation of dosing. A total of 243 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients were randomized (3:1) to receive clevudine 30 mg once daily (n=182) or placebo (n=61) for 24 weeks. Patients were followed for a further 24 weeks off therapy. Median serum HBV DNA reductions from baseline at week 24 were 5.10 and 0.27 log10 copies/mL in the clevudine and placebo groups, respectively (P<0.0001). Viral suppression in the clevudine group was sustained off therapy, with 3.73 log10 reduction at week 34 and 2.02 log10 reduction at week 48. At week 24, 59.0% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (less than 300 copies/mL). The proportion of patients who achieved normalization of alanine aminotransferase (ALT) levels was 68.2% in the clevudine group and 17.5% in the placebo group at week 24 (P<0.0001). ALT normalization in the clevudine group was well maintained during post-treatment follow-up period. The incidence of adverse events (AEs) was similar between the clevudine group and the placebo group. No resistance to clevudine was detected with 24 weeks of administration of drug.


CONCLUSIONS
A 24-week clevudine therapy was well tolerated and showed potent and sustained antiviral effect without evidence of viral resistance during treatment period in HBeAg-positive chronic hepatitis B.
Yoo
Byung Chul
BC
Samsung Medical Center, Sungkyunkwan University, and Yonsei University Hospital, Seoul, Korea.
Kim
Ju Hyun
JH
Chung
Young-Hwa
YH
Lee
Kwan Sik
KS
Paik
Seung Woon
SW
Ryu
Soo Hyung
SH
Han
Byung Hoon
BH
Han
Joon-Yeol
JY
Byun
Kwan Soo
KS
Cho
Mong
M
Lee
Heon-Ju
HJ
Kim
Tae-Hun
TH
Cho
Se-Hyun
SH
Park
Joong-Won
JW
Um
Soon-Ho
SH
Hwang
Seong Gyu
SG
Kim
Young Soo
YS
Lee
Youn-Jae
YJ
Chon
Chae Yoon
CY
Kim
Byung-Ik
BI
Lee
Young-Suk
YS
Yang
Jin-Mo
JM
Kim
Haak Cheoul
HC
Hwang
Jae Seok
JS
Choi
Sung-Kyu
SK
Kweon
Young-Oh
YO
Jeong
Sook-Hyang
SH
Lee
Myung-Seok
MS
Choi
Jong-Young
JY
Kim
Dae-Ghon
DG
Kim
Yun Soo
YS
Lee
Heon Young
HY
Yoo
Kwon
K
Yoo
Hee-Won
HW
Lee
Hyo-Suk
HS
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006509:Hepatitis B / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D010919:Placebos; D001086:Arabinofuranosyluracil; D000410:Alanine Transaminase; C034935:clevudine