Safety and Efficacy of Adefovir Dipivoxil in Children and Adolescents With Chronic Hepatitis B

NCT ID: NCT00095121

Last Updated: 2012-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 173 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-06-30
• Study Completion Date: 2010-04-30

Brief 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).

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo (PLB)

Participants randomized to receive placebo received placebo during the first 48 weeks of treatment (double-blind phase) and then all eligible participants were administered open-label ADV for the remainder of the study.

Group Type: PLACEBO_COMPARATOR

Placebo (PLB)

Intervention Type: DRUG

Matching placebo

Lamivudine

Intervention Type: DRUG

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.

Adefovir Dipivoxil (ADV)

Participants randomized to receive ADV received ADV during the first 48 weeks of treatment (double-blind phase) and then all eligible participants were administered open-label ADV for the remainder of the study.

Group Type: EXPERIMENTAL

Adefovir Dipivoxil (ADV)

Intervention Type: DRUG

10-mg tablet or 2-mg/mL oral suspension

Lamivudine

Intervention Type: DRUG

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.

Interventions

Placebo (PLB)

Matching placebo

Intervention Type: DRUG

Adefovir Dipivoxil (ADV)

10-mg tablet or 2-mg/mL oral suspension

Intervention Type: DRUG

Lamivudine

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 Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Positive HBsAg >= 6 months prior to randomization and positive HBeAg at screening.
• Serum HBV DNA greater than or equal to 1 x 100,000 copies/mL (PCR assay) at initial or confirmatory screening visit.
• Serum ALT levels greater than or equal to 1.5 x ULN at both initial and confirmatory screening visits.
• Compensated liver disease with anticipated survival greater than 12 months and with the following laboratory and clinical parameters within 4 weeks of baseline: *Prothrombin time less than or equal to 1 second above normal range. *Total bilirubin less than 1.3 mg/dL or normal direct bilirubin. *Serum albumin greater than 3 g/dL (greater than 30 g/L). *No clinical history of ascites, variceal bleeding, encephalopathy or splenomegaly. *Adequate renal function defined as creatinine clearance greater than or equal to 80 mL/min (calculated using Schwartz Formula).

Exclusion Criteria

• Received immunoglobulin, interferon or lamivudine therapy within 6 months prior to initial screening visit.
• Participated in any investigational trial with any investigational compound within 2 months prior to initial screening.
• Organ or bone marrow transplant recipients.
• Clinical evidence of decompensated liver disease.
• A Child-Pugh-Turcotte score greater than 6.
• Inability to comply with study requirements.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Flaherty, PharmD

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Boston, Massachusetts, United States

Countries

United States

References

Sokal, E, Kelly, D, et al. The Pharmacokinetics (PK) and Safety of a Single Dose of Adefovir Dipivoxil (ADV) in Children and Adolescents (Aged 2-17) with Chronic Hepatitis B. JHepatol,Vol 40(Suppl 1), P. 132, 2004.

Reference Type: BACKGROUND

Related Links

http://www.gilead.com

Related Info

http://www.gileadclinicaltrials.com/pdf/GS-US-103-0518_48wk_synopsis.pdf

Study Results

Other Identifiers

GS-US-103-0518

Identifier Type: -

Identifier Source: org_study_id