Phase 3
Completed N=266
A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Positive Chronic Hepatitis B
Source: ClinicalTrials.gov NCT00116805 ↗Enrolled (actual)
266
Serious AEs
12.5%
Results posted
May 2010
Primary outcomePrimary: Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48 — 66.5; 12.2 percentage of participants — p=<0.001
Summary
The primary objectives of this study are to compare the efficacy, safety, and tolerability of tenofovir disoproxil fumarate (TDF) versus adefovir dipivoxil (ADV) for the treatment of HBeAg-positive chronic hepatitis B. Participants will receive TDF or ADV for 48 weeks (double-blind). After 48 weeks, eligible participants switched to open-label TDF for up to 480 weeks.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With HBV DNA < 400 Copies/mL and Histological Improvement (2-point Reduction in Knodell Necroinflammatory Score Without Worsening in Knodell Fibrosis Score) at Week 48 |
66.5; 12.2 | <0.001 sig |
| SECONDARY Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48 |
76.1; 13.3 | <0.001 sig |
| SECONDARY Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96 |
77.6; 77.9 | 0.801 |
| SECONDARY Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 |
71.7; 70.5; 67.9; 71.6; 63.4; 66.3 | — |
| SECONDARY Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480 |
93.0; 100.0; 98.0; 96.6 | — |
| SECONDARY Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 |
-6.17; -3.93; -6.26; -6.38; -6.32; -6.31 | — |
| SECONDARY Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 |
-0.10; -2.43; -0.19; -2.27; -0.20; -2.41 | — |
| SECONDARY Percentage of Participants With Histological Response at Week 48 |
74.4; 67.8; 25.6; 32.2 | 0.320 |
| SECONDARY Percentage of Participants With Histological Response at Week 240 |
88.2; 89.6; 11.8; 10.4 | — |
| SECONDARY Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48 |
-3.6; -3.2; -2.7; -2.6 | — |
| SECONDARY Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240 |
-4.8; -5.1; -4.1; -4.5 | — |
| SECONDARY Ranked Assessment of Necroinflammation and Fibrosis at Week 48 |
81.3; 78.9; 4.5; 3.3; 3.4; 5.6 | — |
| SECONDARY Ranked Assessment of Necroinflammation and Fibrosis at Week 240 |
96.1; 97.9; 3.9; 2.1; 0; 0 | — |
| SECONDARY Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48 |
68.0; 54.4 | 0.032 sig |
| SECONDARY Percentage of Participants With ALT Normalization at Week 96 |
65.2; 74.4 | 0.100 |
| SECONDARY Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 |
60.2; 67.8; 59.6; 69.4; 50.0; 65.9 | — |
| SECONDARY Percentage of Participants With ALT Normalization at Weeks 432 and 480 |
79.6; 78.6; 75.0; 82.8 | — |
| SECONDARY Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 |
-107.2; -106.1; -107.8; -120.4; -100.7; -126.2 | — |
| SECONDARY Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 |
-2.0; -6.9; -0.4; -0.7; -1.3; -7.8 | — |
| SECONDARY Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss/Seroconversion at Week 48 |
22.2; 17.5; 20.9; 17.5 | 0.245 |
| SECONDARY Percentage of Participants With HBeAg Loss or Seroconversion to Anti-HBe at Week 96 |
25.9; 25.6; 22.8; 22.0 | 0.963 |
| SECONDARY Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion at Week 48 |
3.2; 0; 1.3; 0 | 0.018 sig |
| SECONDARY Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Week 96 |
5.3; 5.8; 4.1; 4.7 | 0.757 |
| SECONDARY Percentage of Participants With HBsAg Loss or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 |
7.5; 8.0; 5.2; 6.8; 9.4; 7.9 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) |
31; 75; 2; 8; 13; 17 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) |
18; 13; 16; 10; 2; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) |
2; 7; 5; 5; 1; 2 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) |
2; 5; 1; 1; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) |
3; 3; 0; 1; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) |
3; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) |
1; 0; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) |
1; 0; 2; 2; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) |
1; 3; 0; 1; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) |
0; 3; 1; 0; 0; 0 | — |
Eligibility Criteria
Key Inclusion Criteria
A patient must meet all of the following inclusion criteria to be eligible for participation in this study:
- Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B s-antigen (HBsAg) for more than 6 months
- 18 through 69 years of age, inclusive
- Active hepatitis B e-antigen (HBeAg) positive chronic HBV infection, with all of the following:
- HBeAg positive at screening
- Alanine aminotransferase (ALT) levels > 2 × ULN and ≤ 10 × the upper limit of the normal range (ULN)
- Serum HBV DNA > 1 million copies/mL at screening
- creatinine clearance ≥ 70 mL/min
- hemoglobin ≥ 8 g/dL
- neutrophils ≥ 1,000 /mL
- Knodell necroinflammatory score ≥ 3 and a Knodell fibrosis score 12 weeks
- Nucleoside naïve, ie, no prior nucleoside (any nucleoside) therapy for > 12 weeks
- Willing and able to provide written informed consent
- Liver biopsy performed within 6 months of baseline and has readable biopsy slides or agrees to have a biopsy performed prior to baseline
Key Exclusion Criteria
A patient who meets any of the following exclusion criteria is not to be enrolled in this study:
- Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study
- Males and females of reproductive potential who are unwilling to use an effective method of contraception during the study; for males, condoms should be used and for females, a barrier contraception method should be used
- Decompensated liver disease defined as conjugated bilirubin > 1.5 x ULN, prothrombin time (PT) > 1.5 x ULN, platelets 50 ng/mL
- Coinfection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis delta virus (HDV)
- Significant renal, cardiovascular, pulmonary, or neurological disease
- Received solid organ or bone marrow transplantation
- Is currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion
- Has proximal tubulopathy
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT00116805). 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. Informational only — not medical advice.