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.

• Register: EUCTR
• Last refreshed on: 10 February 2014
• Main ID: EUCTR2005-003136-22-DE
• Date of registration: 27/12/2005
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences Incorporated
• Public title: 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.
• Scientific title: 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.
• Date of first enrolment: 05/05/2006
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003136-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Double dummy If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Germany, Spain

Key inclusion & exclusion criteria

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).
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Hepatitis B
MedDRA version: 8.1 Level: LLT Classification code 10008910 Term: Chronic hepatitis B

Intervention(s)

Trade Name: Viread
Product Name: Viread
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: tenofovir disoproxil fumarate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Truvada
Product Name: Truvada
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: tenofovir disoproxil fumarate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
INN or Proposed INN: emtricitabine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint is the proportion of subjects with plasma HBV DNA < 169 copies/mL at Week 48.

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.

To evaluate and compare the incidence of drug resistance mutations in HBV DNA polymerase in both treatment arms.

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 ID(s)

GS-US-174-0106