Virological and Clinical Anti-Hepatitis B Virus (HBV) Efficacy of Tenofovir and Emtricitabine in Patients With HIV/HBV co-Infection

HIV Infections Clinical Trial

Official title:

Virological and Clinical Anti-HBV Efficacy of Tenofovir and Emtricitabine in Antiretroviral Naïve Patients With HIV/HBV co-Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00127959
• Other study ID #: IAT-0038-04
• Status: Completed
• Phase: Phase 4
• First received: August 8, 2005
• Last updated: April 23, 2007
• Start date: March 2004
• Est. completion date: August 2006

Study information

• Verified date: April 2007
• Source: International Antiviral Therapy Evaluation Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

This is a randomized multicentre trial of emtricitabine (FTC) versus tenofovir (TDF)/FTC in antiretroviral naive subjects with HIV/HBV co-infection over 48 weeks (Clinical Trial A).

Plus, a 12 week viral kinetic substudy comparing a subgroup of patients on Clinical Trial A is being conducted. (Substudy A1)

Description:

This is a randomized multicentre trial of FTC vs TDF/FTC in antiretroviral naive subjects with HIV/HBV co-infection over 48 weeks (Clinical Trial A).

Plus, a 12 week viral kinetic substudy comparing a subgroup of patients on Clinical Trial A is being conducted. (Substudy A1)

Primary Objectives:

• To compare the proportion of subjects with HBV DNA levels below the limit of detection (<400 copies/ml) by week 48 in each treatment group

Secondary Objectives:

• To evaluate the emergence of HBV resistance at 48 weeks

• To compare the proportion of patients with undetectable HBV DNA at weeks 12 and 24 in each treatment group

• To compare the proportion of patients who achieve HBeAg and HBsAg seroconversion at weeks 12, 24 and 48 during the study

• To compare changes in ALT from baseline and the rate of hepatic cytolysis (ALT>5x ULN)

• To compare suppression of HIV-1 RNA and changes in CD4/CD8 counts over 48 weeks

• To compare the effect of therapy on histological changes in the liver and the presence of ccc-DNA

Enrollment:

• 24 patients in Clinical trial A (of whom 16 enter substudy A1).

Clinical Trial A:

• Patients with HIV/HBV co-infection who are naive to HIV/HBV therapy, have detectable HBV viraemia and are willing to start antiretroviral therapy.

Inclusion Criteria:

• Written informed consent

• Documented HIV infection

• Age 18 – 70 years

• HBV DNA > 106 copies/ml

Randomization:

• Arm 1: Zidovudine (AZT), emtricitabine (FTC), efavirenz (EFV)

• Arm 2: Tenofovir (TDF), emtricitabine (FTC), efavirenz (EFV)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Written informed consent

• Documented HIV infection

• Age 18 – 70 years

• HBV DNA > 10E6 copies/ml

• ALT < 10 x ULN (upper limit of normal)

• Creatinine <= 2.0mg/dl

• Platelet count >= 50,000/mm3

• HIV-1 therapy naive

• No prior exposure to anti-HBV agents

Exclusion Criteria:

• Hepatitis C viral RNA (CV-RNA) positive or Anti-hepatitis A virus immunoglobulin M (HAV IgM) positive

• Acute hepatitis (serum ALT > 1000 U/L)

• Prior LAM, TDF, or adefovir dipivoxil (ADV) therapy

• Active opportunistic infection

• Pregnancy or lactation

• Other chronic liver disease

• Concurrent malignancy requiring cytotoxic chemotherapy

• Decompensated or Child’s C cirrhosis

• Alfa-fetoprotein (AFP) > 3X ULN (unless negative computed tomography [CT] scan or magnetic resonance imaging [MRI] within 3 months of entry date)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Communicable Diseases
• Hepatitis
• Hepatitis A
• Hepatitis B
• HIV Infections
• Infection

Intervention

Drug:
• tenofovir

• emtricitabine

• zidovudine

• efavirenz

Locations

Country	Name	City	State
Netherlands	Academic Medical Center	Amsterdam	NH

Sponsors (2)

Lead Sponsor	Collaborator
International Antiviral Therapy Evaluation Center	Gilead Sciences

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HBV DNA suppression as measured by comparison of area under the curve (AUC) measurements after 48 weeks therapy
Secondary	Proportion of patients with undetectable HBV DNA in serum
Secondary	Rate of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) seroconversion
Secondary	Rate of emergence of lamivudine (LAM)-resistant HBV genotypes
Secondary	Suppression of plasma HIV-RNA (< 50 copies/ml)
Secondary	Changes in CD4+ /CD8+ cell counts
Secondary	Presence of covalently closed circle DNA (cccDNA) on liver biopsy