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.
Dr Hyo-Suk Lee and colleagues assessed the degree and durability of the antiviral response to 12 weeks of clevudine treatment.
The research team investigated its safety and tolerability.
A total of 98 patients with Hep B e antigen-positive chronic Hepatitis B were included.
The team randomized 32 patients to placebo, 32 to receive 30-mg clevudine, and 34 receiving 50-mg clevudine.
|Hep B virus DNA reduced from baseline at week 12 by about 4.5 with treatment|
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 0.2 in the placebo group vs about 4.5 with the clevudine treatment groups.
The researchers noted that posttreatment antiviral activities were sustained.
Antiviral activities were reduced by 3.3 and 3 log10 reductions at week 12 off-therapy.
The team observed 2.3 and 1.4 log10 reductions in antiviral activity at week 24 off-therapies in the 30- and 50-mg clevudine groups, respectively.
Median serum alanine aminotransferase levels decreased markedly from baseline during clevudine treatment.
The team found that alanine aminotransferase levels were maintained below the upper limit of normal during the weeks off-therapy in both clevudine-treated groups.
The incidences of adverse events and treatment-emergent grade 3 or 4 laboratory abnormalities were similar for the 3 groups.
Dr Lee's team concluded, “Clevudine showed potent antiviral activity during therapy and induced a sustained posttreatment antiviral effect for 6 months after a 12-week treatment period.”
“This was associated with a sustained normalization of alanine aminotransferase levels levels.”