A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg-positive chronic hepatitis B.
Clevudine is a nucleoside analog with an unnatural beta-L configuration. In a phase I/II clinical trial, once daily doses ranging from 10 to 200 mg for 28 days were well tolerated, and produced significant antiviral activity. The present study was conducted to assess the degree and durability of the antiviral response to 12 weeks of clevudine treatment, and to investigate its safety and tolerability. A total of 98 patients with HBeAg-positive chronic hepatitis B were randomized to placebo (n=32), 30-mg clevudine (n=32), and 50-mg clevudine (n=34) groups. Patients were followed up after 12 weeks of treatment for a further 24 weeks off-therapy. Median serum hepatitis B virus DNA reductions from baseline at week 12 were 0.20, 4.49, and 4.45 log10 copies/mL in the placebo, 30-mg clevudine, and 50-mg clevudine groups, respectively (P < .0001). Posttreatment antiviral activities were sustained, with 3.32 and 2.99 log10 reductions at week 12 off-therapy and 2.28 and 1.40 log10 reductions at week 24 off-therapies in the 30- and 50-mg clevudine groups, respectively. Median serum alanine aminotransferase (ALT) levels decreased markedly from baseline during clevudine treatment and were maintained below the upper limit of normal throughout the 24 weeks off-therapy in the two clevudine-treated groups. The incidences of adverse events and treatment-emergent grade 3 or 4 laboratory abnormalities were similar for the three groups. In conclusion, clevudine showed potent antiviral activity during therapy and induced a sustained posttreatment antiviral effect for 6 months after a 12-week treatment period, and this was associated with a sustained normalization of ALT levels.
Lee
Hyo-Suk
HS
Seoul National University Hospital, South Korea. hsleemd@snu.ac.kr
Chung
Young-Hwa
YH
Lee
Kwansik
K
Byun
Kwan Soo
KS
Paik
Seung Woon
SW
Han
Joon-Yeol
JY
Yoo
Kwon
K
Yoo
Hee-Won
HW
Lee
Jin Heon
JH
Yoo
Byung Chul
BC
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D013997:Time Factors
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D001086:Arabinofuranosyluracil; C034935:clevudine