A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg-positive chronic hepatitis B

Hyo Suk Lee, Young Hwa Chung, Kwan Sik Lee, Kwan Soo Byun, Woon Paik Seung, Joon Yeol Han, Kwon Yoo, Hee Won Yoo, Heon Lee Jin, Chul Yoo Byung

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Clevudine is a nucleoside analog with an unnatural β-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.

Original languageEnglish
Pages (from-to)982-988
Number of pages7
JournalHepatology
Volume43
Issue number5
DOIs
Publication statusPublished - 2006 May 1

Fingerprint

Hepatitis B e Antigens
Chronic Hepatitis B
Antiviral Agents
Therapeutics
Alanine Transaminase
Placebos
Clevudine
Phase II Clinical Trials
Clinical Trials, Phase I
Serum
Nucleosides
Hepatitis B virus
Safety

ASJC Scopus subject areas

  • Hepatology

Cite this

A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg-positive chronic hepatitis B. / Lee, Hyo Suk; Chung, Young Hwa; Lee, Kwan Sik; Byun, Kwan Soo; Seung, Woon Paik; Han, Joon Yeol; Yoo, Kwon; Yoo, Hee Won; Jin, Heon Lee; Byung, Chul Yoo.

In: Hepatology, Vol. 43, No. 5, 01.05.2006, p. 982-988.

Research output: Contribution to journalArticle

Lee, HS, Chung, YH, Lee, KS, Byun, KS, Seung, WP, Han, JY, Yoo, K, Yoo, HW, Jin, HL & Byung, CY 2006, 'A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg-positive chronic hepatitis B', Hepatology, vol. 43, no. 5, pp. 982-988. https://doi.org/10.1002/hep.21166
Lee, Hyo Suk ; Chung, Young Hwa ; Lee, Kwan Sik ; Byun, Kwan Soo ; Seung, Woon Paik ; Han, Joon Yeol ; Yoo, Kwon ; Yoo, Hee Won ; Jin, Heon Lee ; Byung, Chul Yoo. / A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg-positive chronic hepatitis B. In: Hepatology. 2006 ; Vol. 43, No. 5. pp. 982-988.
@article{2171255ad0694a52ba8298ff37e4572c,
title = "A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg-positive chronic hepatitis B",
abstract = "Clevudine is a nucleoside analog with an unnatural β-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.",
author = "Lee, {Hyo Suk} and Chung, {Young Hwa} and Lee, {Kwan Sik} and Byun, {Kwan Soo} and Seung, {Woon Paik} and Han, {Joon Yeol} and Kwon Yoo and Yoo, {Hee Won} and Jin, {Heon Lee} and Byung, {Chul Yoo}",
year = "2006",
month = "5",
day = "1",
doi = "10.1002/hep.21166",
language = "English",
volume = "43",
pages = "982--988",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "5",

}

TY - JOUR

T1 - A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg-positive chronic hepatitis B

AU - Lee, Hyo Suk

AU - Chung, Young Hwa

AU - Lee, Kwan Sik

AU - Byun, Kwan Soo

AU - Seung, Woon Paik

AU - Han, Joon Yeol

AU - Yoo, Kwon

AU - Yoo, Hee Won

AU - Jin, Heon Lee

AU - Byung, Chul Yoo

PY - 2006/5/1

Y1 - 2006/5/1

N2 - Clevudine is a nucleoside analog with an unnatural β-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.

AB - Clevudine is a nucleoside analog with an unnatural β-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.

UR - http://www.scopus.com/inward/record.url?scp=33646585175&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646585175&partnerID=8YFLogxK

U2 - 10.1002/hep.21166

DO - 10.1002/hep.21166

M3 - Article

C2 - 16628625

AN - SCOPUS:33646585175

VL - 43

SP - 982

EP - 988

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 5

ER -