E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008910 |
E.1.2 | Term | Chronic hepatitis B |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To characterize the antiviral activity of tenofovir DF 300 mg QD versus emtricitabine 200 mg/tenofovir DF 300 mg QD in subjects currently being treated with adefovir dipivoxil for CHB who have persistent viral replication. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of tenofovir DF 300 mg QD versus emtricitabine 200 mg/tenofovir DF 300 mg QD in subjects currently being treated with adefovir dipivoxil for CHB who have persistent viral replication.
To evaluate and compare the incidence of drug resistance mutations in HBV DNA polymerase in both treatment arms.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 18 through 69 years of age, inclusive
• Chronic HBV infection, defined as positive serum HBsAg for at least 6 months
• Active chronic HBV infection with all the following:
- Currently treated with adefovir dipivoxil 10 mg QD (for ≥ 24 weeks but ≤ 96 weeks) - HBeAg positive or negative at screening - Plasma HBV DNA ≥ 1000 copies/mL at screening (irrespective of HBeAg status) - Serum ALT < 10 x ULN - Creatinine clearance ≥ 70 mL/min - Hemoglobin ≥ 8 g/dL - Neutrophils ≥ 1,000 /mm3
• Nucleoside-naïve or lamivudine-experienced (≥ 12 weeks of therapy)
• Negative serum ß-HCG
• Compliant with adefovir dipivoxil
• Willing and able to provide written informed consent (Note: individuals who have been committed to an institution by virtue of an order issued either by the courts or by a public authority will not be enrolled in this study). |
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E.4 | Principal exclusion criteria |
• Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.
• Male or females of reproductive potential who are unwilling to use an effective method of contraceptive while enrolled in 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 < 75,000/mm3, serum albumin < 3.0 g/dL, or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy, variceal hemorrhage).
• Prior use of tenofovir DF or entecavir
• Received treatment with interferon or pegylated interferon within 6 months of the screening visit.
• Evidence of HCC; for example, α fetoprotein > 50 ng/mL or by any other standard of care measure.
• Co-infection with HCV (based on serology), HIV, or HDV.
• Significant renal, cardiovascular, pulmonary, or neurological disease.
• Received solid organ or bone marrow transplantation.
• Is currently receiving therapy with immunomodulators (e.g., corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion.
• Has proximal tubulopathy
• Known hypersensitivity to tenofovir DF or emtricitabine/tenofovir DF, tenofovir or emtricitabine or their phosphorylated forms, or study drug product formulation excipients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of subjects with plasma HBV DNA < 169 copies/mL at Week 48. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |