Phase 3
Completed N=382
A Study to Compare Tenofovir Disoproxil Fumarate Versus Adefovir Dipivoxil for the Treatment of HBeAg-Negative Chronic Hepatitis B
Source: ClinicalTrials.gov NCT00117676 ↗Enrolled (actual)
382
Serious AEs
15.1%
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 — 70.8; 48.8; 29.2; 51.2 percentage of participants — p=<0.001
Summary
This 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 pre-core mutant 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 |
70.8; 48.8; 29.2; 51.2 | <0.001 sig |
| SECONDARY Percentage of Participants With HBV DNA < 400 Copies/mL at Week 48 |
93.2; 63.2 | <0.001 sig |
| SECONDARY Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 96 |
90.6; 89.3 | 0.672 |
| SECONDARY Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 144, 192, 240, 288, 336, and 384 |
86.7; 88.4; 84.0; 86.8; 82.8; 83.9 | — |
| SECONDARY Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 432 and 480 |
97.6; 97.7; 100.0; 100.0 | — |
| SECONDARY Change From Baseline in HBV DNA at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 |
-4.57; -4.07; -4.54; -4.74; -4.61; -4.77 | — |
| SECONDARY Change From Week 48 in HBV DNA at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 |
0.02; -0.60; -0.03; -0.63; 0.01; -0.61 | — |
| SECONDARY Percentage of Participants With Histological Response at Week 48 |
72.4; 68.8; 27.6; 31.2 | 0.293 |
| SECONDARY Percentage of Participants With Histological Response at Week 240 |
87.3; 85.1; 12.7; 14.9 | — |
| SECONDARY Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 48 |
-3.5; -3.4; -2.6; -2.6 | — |
| SECONDARY Change From Baseline in Knodell and Ishak Necroinflammatory Scores at Week 240 |
-4.6; -4.9; -4.0; -4.2 | — |
| SECONDARY Ranked Assessment of Necroinflammation and Fibrosis at Week 48 |
82.0; 81.6; 6.8; 8.0; 4.8; 0.8 | — |
| SECONDARY Ranked Assessment of Necroinflammation and Fibrosis at Week 240 |
96.7; 94.6; 2.7; 1.4; 0.7; 4.1 | — |
| SECONDARY Percentage of Participants With ALT Normalization at Week 48 |
76.3; 77.1 | 0.859 |
| SECONDARY Percentage of Participants With ALT Normalization at Weeks 96 |
72.4; 68.5 | 0.359 |
| SECONDARY Percentage of Participants With ALT Normalization at Weeks 144, 192, 240, 288, 336, and 384 |
74.3; 70.0; 68.2; 76.4; 70.3; 75.7 | — |
| SECONDARY Percentage of Participants With ALT Normalization at Weeks 432 and 480 |
86.5; 87.2; 80.0; 88.9 | — |
| SECONDARY Change From Baseline in ALT at Weeks 48, 96, 144, 192, 240, 288, 336, 384, 432, and 480 |
-95.0; -124.4; -93.7; -138.5; -99.1; -140.0 | — |
| SECONDARY Change From Week 48 in ALT at Weeks 96, 144, 192, 240, 288, 336, 384, 432, and 480 |
2.4; -0.6; -0.6; -0.3; 0.7; -3.6 | — |
| SECONDARY Percentage of Participants With Hepatitis B S-Antigen (HBsAg) Loss or Seroconversion Antibody to HBs (Anti-HBs) at Week 48 |
0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Week 96 |
0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With HBsAg Loss and/or Seroconversion to Anti-HBs at Weeks 144, 192, 240, 288, 336, 384, 432, and 480 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 48 (Resistance Surveillance) |
8; 42; 0; 7; 3; 14 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 96 (Resistance Surveillance) |
6; 1; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 144 (Resistance Surveillance) |
4; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 192 (Resistance Surveillance) |
3; 1; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 240 (Resistance Surveillance) |
1; 2; 2; 1; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 288 (Resistance Surveillance) |
3; 1; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 336 (Resistance Surveillance) |
0; 1; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 384 (Resistance Surveillance) |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 432 (Resistance Surveillance) |
2; 0; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants With HBV Genotypic Changes From Baseline at Week 480 (Resistance Surveillance) |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Key Inclusion Criteria
- Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B s-antigen (HBsAg) for at least 6 months.
- 18 through 69 years of age, inclusive.
- Active hepatitis B e-antigen (HBeAg) negative chronic HBV infection, with all of the following:
- HBeAg negative and HBeAb positive at screening
- Alanine aminotransferase (ALT) levels > the upper limit of the normal range (ULN) and ≤ 10 x ULN
- Serum HBV DNA > 100, 000 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 prior lamivudine experience will be eligible
- Willing and able to provide written informed consent
- Had a 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
- Pregnant women, women who are breast feeding, or women 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.
- Decompensated liver disease defined as conjugated bilirubin > 1.5 x ULN, prothrombin time (PT) > 1.5 x ULN, platelets < 75,000/mL, serum albumin < 3.0 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage)
- Received any nucleoside, nucleotide (TDF or ADV) or interferon (pegylated or not) therapy within 6 months prior to the pre treatment biopsy
- Evidence of hepatocellular carcinoma (HCC)
- Coinfection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D 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 (NCT00117676). 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.