Phase 3
N=173
Safety and Efficacy of Adefovir Dipivoxil in Children and Adolescents With Chronic Hepatitis B
Chronic Hepatitis B
Bottom Line
View on ClinicalTrials.gov: NCT00095121 ↗Enrolled (actual)
173
Serious AEs
7.5%
Results posted
Jun 2011
Primary outcome: Primary: Percentage of Participants With Serum Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 1000 Copies/mL (Polymerase Chain Reaction [PCR]-Based Assay) and Normal Alanine Aminotransferase (ALT) at Week 48 (Missing = Failure) — 0; 0; 5; 0 percentage of participants — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Placebo (PLB) (Drug); Adefovir Dipivoxil (ADV) (Drug); Lamivudine (Drug)
- Age
- Pediatric · 2+ yrs
- Sex
- All
- Sponsor
- Gilead Sciences
- Primary completion
- May 2006
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Serum Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < 1000 Copies/mL (Polymerase Chain Reaction [PCR]-Based Assay) and Normal Alanine Aminotransferase (ALT) at Week 48 (Missing = Failure) |
0; 0; 5; 0; 19; 2 | <0.001 sig |
| SECONDARY Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Baseline) |
0; 0 | — |
| SECONDARY Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment - Missing = Failure) (ADV Week 192) |
15; 15 | — |
| SECONDARY Percentage of Participants With Serum HBV DNA < 1000 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Week 240) |
6 | — |
| SECONDARY Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Baseline) |
0; 0 | — |
| SECONDARY Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Week 192) |
11; 13 | — |
| SECONDARY Percentage of Participants With Serum HBV DNA < 400 Copies/mL (PCR-based Assay) While on Treatment (Missing = Failure) (ADV Week 240) |
6 | — |
| SECONDARY Adefovir (ADV) Baseline Serum HBV DNA |
8.76; 8.24 | — |
| SECONDARY Change From ADV Baseline to ADV Week 192 for Serum HBV DNA |
-5.89; -5.41 | — |
| SECONDARY Change From ADV Baseline to ADV Week 240 for Serum HBV DNA |
-5.87 | — |
| SECONDARY ADV Baseline ALT |
108.69; 99.81 | — |
| SECONDARY Change From ADV Baseline to ADV Week 192 for ALT |
-66.06; -38.88 | — |
| SECONDARY Change From ADV Baseline to ADV Week 240 for ALT |
-64.33 | — |
| SECONDARY Percentage of Participants With Normal ALT at Adefovir Baseline (Missing = Failure) |
7; 15 | — |
| SECONDARY Percentage of Participants With Normal ALT at ADV Week 192 (Missing = Failure) |
14; 13 | — |
| SECONDARY Percentage of Participants With Normal ALT at ADV Week 240 (Missing = Failure) |
5 | — |
| SECONDARY Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss or Seroconversion by End of Blinded Treatment (Study Week 48; Randomized and Treated Analysis Set) |
17; 5; 16; 5 | 0.051 |
| SECONDARY Percentage of Participants With HBeAg Loss or Seroconversion by ADV Week 192 (Open Label Analysis Set, Participants Who Were HBeAg Positive at ADV Baseline; Missing = Excluded) |
56; 33; 44; 11 | — |
| SECONDARY Percentage of Participants With HBeAg Loss or Seroconversion by ADV Week 240 (Open Label Analysis Set, Participants Who Were HBeAg Positive at ADV Baseline; Missing = Excluded) |
33; 17 | — |
| SECONDARY Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) |
48; 18; 17; 12; 3; 3 | — |
| SECONDARY Cumulative Summary of Participants With HBV Genotypic Changes From Baseline (Resistance Surveillance) for Subjects Who Received Combination ADV + Lamivudine Therapy |
5; 1; 3; 1; 3; 1 | — |
| SECONDARY Percentage of Participants With Durable HBeAg Seroconversion |
82; 71 | — |
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.
Eligibility Criteria
Key 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).
Key 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.
Data sourced from ClinicalTrials.gov (NCT00095121). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.