Safety and Efficacy of Adefovir Dipivoxil in Children and Adolescents With Chronic Hepatitis B
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to investigate the efficacy and safety of adefovir dipivoxil for
      the treatment of chronic hepatitis B in children and adolescents (age 2 to less than 18
      years) following 48 weeks of placebo-controlled, double-blind treatment and following an
      additional 192 weeks of open-label adefovir dipivoxil treatment.
    

Detailed description: 
      Weeks 1 through 48 (Study Year 1): The first 48 weeks of the study were a randomized,
      double-blind, placebo-controlled, parallel-group treatment period. Participants were randomly
      assigned to treatment in a 2:1 fashion to ADV or PLB. Prior to randomization, eligible
      participants were classified into 1 of 6 strata based upon age at screening (2 to < 7 years;
      >= 7 to < 12 years; >= 12 to < 18 years) and prior exposure to treatment for chronic
      hepatitis B (CHB) (prior treatment; no prior treatment).

      Weeks 49 through 240 (Study Years 2 through 5): At Week 48, all placebo-treated participants
      who did not exhibit HBeAg or hepatitis B surface antigen (HBsAg) seroconversion at Week 44,
      plus all ADV-treated participants, were offered the opportunity to receive open-label ADV for
      up to an additional 192 weeks. Any participant with HBV DNA >= 1000 copies/mL at 2
      consecutive visits 12 weeks apart was to be discontinued from open-label study treatment. The
      only exception was for participants in the adolescent age range with prior lamivudine
      experience who were allowed the opportunity to add lamivudine to ADV; similarly, if
      combination failed to impart suppression of HBV DNA below 1000 copies/mL (confirmed)
      discontinuation was necessary. All participants who discontinued study drug due to confirmed
      seroconversion were requested to continue to return for study visits for the remainder of the
      study in order to evaluate the durability of seroconversion. Participants who wished to
      discontinue study treatment and withdraw from the study prior to study completion were
      requested to return every 4 weeks for 16 weeks for posttreatment evaluations following an
      early termination visit. Any participants who experienced posttreatment hepatic flares during
      the 16-week follow-up period were to be followed every 4 weeks until their ALT levels
      returned to <= 2 times the upper limit of normal (ULN) for a maximum off-treatment follow-up
      of 6 months. Participants who experienced a severe hepatic flare (per protocol definition)
      after discontinuation of ADV during the open-label treatment period may have been eligible to
      receive ADV for treatment of the hepatic flare (after consultation with the Gilead medical
      monitor).
    

Intervention name(s): Placebo (PLB); Adefovir Dipivoxil (ADV); Lamivudine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Matching placebo; 10-mg tablet or 2-mg/mL oral suspension; 100-mg tablet administered according to package labeling. Lamivudine was to be added to the open-label ADV regimen of subjects with a serum HBV DNA concentration >= 1000 copies/mL at 2 consecutive study visits at or after Study Week 96. If the HBV DNA concentration remained >= 1000 copies/mL at 2 consecutive study visits after the addition of lamivudine, the investigator was required to discontinue all study drugs, perform the early termination ssessments, and have the subject return every 4 weeks for 16 weeks of posttreatment evaluations.
Intervention MeSH terms: Lamivudine; Adefovir; Adefovir dipivoxil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Hepatitis B; Children; Pediatric; Adefovir Dipivoxil