Phase 2
Completed N=126
A Study to Compare Tenofovir DF Versus the Combination of Emtricitabine Plus Tenofovir DF for the Treatment of Chronic Hepatitis B in Patients With Normal Alanine Aminotransferase (ALT)
Source: ClinicalTrials.gov NCT00507507 ↗Enrolled (actual)
126
Serious AEs
5.0%
Results posted
Aug 2013
Primary outcomePrimary: Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192 — 54.7; 75.8 percentage of participants — p=0.016
Summary
The main objective of the study was to evaluate the antiviral activity of tenofovir disoproxil fumarate (tenofovir DF) monotherapy versus emtricitabine (FTC) plus tenofovir DF combination therapy for the treatment of chronic hepatitis B (HBV) in participants in the immune tolerant phase of HBV infection.
The efficacy of tenofovir DF monotherapy versus FTC plus tenofovir DF combination therapy was evaluated for suppression of the virus (decrease in HBV DNA), serological response (generation of antibodies to the virus), biochemical response (changes in liver enzymes), and the development of drug-resistant mutations. The safety and tolerability of both tenofovir DF monotherapy and FTC plus tenofovir DF were evaluated by routine monitoring for adverse events and changes in laboratory parameters.
Participants were randomized in a 1:1 ratio to receive tenofovir DF monotherapy or FTC plus tenofovir DF. All subjects were to continue on blinded study medication until the last subject reached Week 192. Participants who permanently discontinued study drug (on or before Week 192) were followed for a 24-week treatment-free follow-up period, or until initiation of alternative HBV therapy, whichever occurred first. Subjects who discontinued study drug on or after Week 48 because of hepatitis B surface antigen (HBsAg) loss or seroconversion to antibody to hepatitis B surface antigen (anti-HBs), however, were to have returned for their regularly scheduled through Week 192 and every 16 weeks thereafter until the last subject reached Week 192.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192 |
54.7; 75.8 | 0.016 sig |
| SECONDARY Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144 |
40.6; 59.7; 53.1; 75.8; 62.5; 80.6 | 0.050 |
| SECONDARY Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192 |
29.7; 33.9; 45.3; 64.5; 50.0; 72.6 | 0.703 |
| SECONDARY Change From Baseline in HBV DNA at Week 48 |
-6.22; -6.49 | 0.010 sig |
| SECONDARY Change From Baseline in HBV DNA at Week 96 |
-6.46; -6.55 | 0.019 sig |
| SECONDARY Change From Baseline in HBV DNA at Week 144 |
-6.66; -6.62 | 0.186 |
| SECONDARY Change From Baseline in HBV DNA at Week 192 |
-6.32; -6.70 | 0.070 |
| SECONDARY Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192 |
52; 54; 52; 50; 51; 46 | 0.467 |
| SECONDARY Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192 |
0; 0; 2; 0; 4; 0 | 0.496 |
| SECONDARY Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192 |
0; 0; 2; 0; 4; 0 | 0.496 |
| SECONDARY Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Occurrence of HBV Resistance Mutations |
6; 5; 16; 9 | — |
Eligibility Criteria
Inclusion Criteria
- Chronic HBV infection, defined as positive serum HBsAg for at least 6 months or HBsAg positive > 3 months and positive for immunoglobulin G antibody against hepatitis B core antigen
- 18 through 69 years of age, inclusive
- Hepatitis B e antigen (HBeAg) positive
- HBV DNA ≥ 10^8 copies/mL
- ALT ≤ the upper limit of the normal range (ULN)
- Willing and able to provide written informed consent
- Negative serum beta-human chorionic gonadotropin (for females of childbearing potential only)
- Calculated creatinine clearance ≥ 70 mL/min
- Hemoglobin ≥ 10 g/dL
- Neutrophils ≥ 1,500/mm^3
- No prior oral HBV therapy (eg, nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)
Exclusion Criteria
- Pregnant women, women who were breast feeding, or who believed they may have wished to become pregnant during the course of the study
- Males and females of reproductive potential unwilling to use an effective method of contraception during the study
- Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 x ULN, prothrombin time > 1.2 x ULN, platelets 50 ng/mL
- Evidence of hepatocellular carcinoma
- Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus
- Significant renal, cardiovascular, pulmonary, or neurological disease
- Received solid organ or bone marrow transplantation
- Was currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion
- Had proximal tubulopathy
- Known hypersensitivity to the study drugs, the metabolites, or formulation excipients
Data sourced from ClinicalTrials.gov (NCT00507507). 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.