Find A Research Study

This will be a Phase III, randomized, double-blind, parallel-group, active-control, multi-center trial of 96-weeks’ duration. Subjects will be assigned to receive either clevudine 30 mg once daily or adefovir 10 mg once daily for 96 weeks. At Week 48, subjects will be assessed for HBV DNA levels, normalization of ALT, and eAg seroconversion. Subjects will then continue to be followed based on results;
• DISCONTINUE FOR EFFICACY AT WEEK 72: Subjects who achieve efficacy by loss of HBeAg/detection of anti-eAb before or at Week 48 on either the adefovir or clevudine arms will be followed for an additional 24 weeks to assure continued efficacy and will then discontinue blinded therapy at Week 72. These subjects will not receive placebo. These subjects will be followed closely for potential flare.
• CONTINUE THERAPY: Subjects who respond only virologically (<300/mL), but continue to have detectable HBeAg without detectable anti-eAb will continue on blinded therapy.
• DISCONTINUE FOR EFFICACY AFTER WEEK 72: Subjects who have detectable eAg at Week 48, but subsequently demonstrate loss of eAg/detection of anti-eAb (at or before Week 60)will be followed for an additional 24 weeks after first documentation of eAg loss/detection of anti-eAb, and then may discontinue blinded therapy, as per recent practice guidelines.
• DISCONTINUE FOR FAILURE: Subjects who have not achieved a > 2 log decrease in HBV DNA by Week 24 will be considered treatment failures. Subjects whose HBV VL is suppressed below the level of detection (<300 copies/mL) and rebounds to > 1 log from nadir (“Rebounders”) on two separate occasions (confirmation VL required) will also be considered treatment failures. Subjects whose HBV DNA remains >1000 copies/mL at Weeks 48 or 96 will also be considered treatment failures. Preclinical in vitro viral susceptibility testing shows a reduction in the potency of clevudine when the N236T mutation, which can be selected during adefovir therapy, is present. Therefore, subjects meeting failure criteria will not be permitted to switch to the alternate blinded therapy and should be switched to an approved anti-HBV drug, as determined by the investigator and based upon the preclinical viral susceptibility data.

All subjects will have liver biopsies performed at screening (or within 6 months prior to the Baseline visit) and at Week 48 for histology and intrahepatic cccDNA quantitation. Subjects will also be asked to consider undergoing a liver biopsy at Week 96.

Subjects completing the 96 week trial will be eligible to continue participating in a rollover study for long-term evaluation of safety, efficacy, and durability of viral suppression on or off of therapy.

Any subject withdrawing from therapy will be followed for safety and viral load for a minimum of 6 months.

(No information)