E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008910 |
E.1.2 | Term | Chronic hepatitis B |
|
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 compare the antiviral efficacy against hepatitis B virus (HBV) of tenofovir DF monotherapy versus tenofovir DF plus emtricitabine combination therapy |
|
E.2.2 | Secondary objectives of the trial |
•To evaluate the safety and tolerability of tenofovir DF versus tenofovir DF plus emtricitabine combination therapy •To evaluate the biochemical and serological response to tenofovir DF monotherapy versus tenofovir DF plus emtricitabine combination therapy •To compare the incidence of drug resistant mutations between treatment arms
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Chronic HBV infection, defined as positive serum HBsAg for at least 6 months or HBsAg positive > 3 months and negative for IgM anti-HBc •18 through 69 years of age, inclusive •HBeAg positive •HBV DNA ≥ 108 copies/mL •ALT ≤ ULN •Willing and able to provide written informed consent •Negative serum β HCG (for females of childbearing potential only) •Calculated creatinine clearance ≥ 70 mL/min by the following formula: (140-age in years) (body weight [kg]) (72) (serum creatinine [mg/dl]) [Note: multiply estimated rate by 0.85 for women]
•Hemoglobin ≥ 10 g/dL •Neutrophils ≥ 1,500 /mm3 •No prior oral HBV therapy (e.g., nucleotide and/or nucleoside therapy or other investigational agents for HBV infection).
|
|
E.4 | Principal exclusion criteria |
•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 not willing 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 in combination with one other form of contraception. •Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 x ULN, PT > 1.2 x ULN, platelets < 150,000/mm3, serum albumin < 3.5 g/dL, or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy, variceal hemorrhage). •Received interferon (pegylated or not) therapy within 6 months of the screening visit •α fetoprotein > 50 ng/mL •Evidence of hepatocellular carcinoma (HCC) •Co infection with HCV (by 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 susceptible of modifying renal excretion. •Has proximal tubulopathy. •Known hypersensitivity to the study drugs, the metabolites or formulation excipients.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
•The primary endpoint is HBV DNA < 400 copies/mL. Using group sequential testing for the primary efficacy analysis, the primary efficacy endpoint will be evaluated after the last subject reaches Week 48 and every 48 weeks thereafter. |
|
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
|
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
|
As per protocol the trial will be completed when the last patient randomized completes the week 144 visit |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |