A Phase 2, Randomized, Double-Blind Study Exploring the Efficacy, Safety and Tolerability of Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus Emtricitabine plus Tenofovir DF Fixed-Dose Combination Therapy in Subjects Currently Being Treated with Adefovir Dipivoxil for Chronic Hepatitis B and having Persistent Viral Replication. Estudio aleatorizado de fase 2 a doble ciego para evaluar la eficacia, seguridad y tolerabilidad de la monoterapia de tenofovir disoproxil fumarato (DF) en comparación con la terapia combinada de emtricitabina más tenofovir DF a dosis fija, en pacientes que reciben adefovir dipivoxil en la actualidad para el tratamiento de la hepatitis B crónica y presentan replicación viral persistente

Phase 1

• Conditions: Chronic Hepatitis B Hepatitis B crónica; MedDRA version: 8.1Level: LLTClassification code 10008910Term: Chronic hepatitis B

• Registration Number: EUCTR2005-003136-22-ES
• Lead Sponsor: Gilead Sciences Incorporated

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2006-01-26
• Study Completion: 2010-10-05
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 90

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 (greater than or equal to 12 weeks of therapy)

• Negative serum ß-HCG

• Compliant with adefovir dipivoxil

• Willing and able to provide written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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, a 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.;Secondary Objective: 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.<br><br>To evaluate and compare the incidence of drug resistance mutations in HBV DNA polymerase in both treatment arms.<br>;Primary end point(s): The primary endpoint is the proportion of subjects with plasma HBV DNA <169 copies/mL at week 48.