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Efficacy of Tenofovir and Emtricitabine in ARV-naive Patients With HIV/HBV Co-infection

Primary Purpose

Hepatitis B Virus, HIV Infections

Status

Completed

Phase

Phase 2

Locations

Thailand

Study Type

Interventional

Intervention

Emtricitabine

About this trial

This is an interventional treatment trial for Hepatitis B Virus focused on measuring TDF+FTC, FTC, HIV/HBV, TDF compared to TDF+FTC in HIV/HBV, Treatment Naive

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Written informed consent
Documented HIV infection (positive serology for HIV-1 and detectable HIV-1 RNA)
Age 18 - 70 years
HBV DNA > 106 copies/ml
HBsAg positive for > 6 months

In case documented duration of HBsAg seropositive is less than 6 months (this situation is most likely to occur in patients newly presenting to the HIV-outpatient clinic) the patient is eligible if the patient is:

HBsAg positive and
HBc core IgM antibody negative and
the liver biopsy gives evidence for a chronic active hepatitis. Thus making it likely that this patient has acquired the HBV infection more than 6 months ago.
- ALT < 10 x ULN
- Creatinine <= 2.0mg/dl
- Platelet count >= 50,000/mm3
- HIV-1 therapy naive
- No prior exposure to anti-HBV agents (LAM, adefovir, TDF) although prior IFN treatment allowed

Exclusion Criteria:

HCV-RNA positive or Anti-HAV IgM positive
Acute hepatitis (serum ALT > 1000 U/L)
Prior LAM, TDF, or ADV therapy
Active opportunistic infection
Other causes of chronic liver disease identified ( autoimmune hepatitis, haemochromatosis, Wilsons disease, alfa-1-antitrypsin deficiency)
Concurrent malignancy requiring cytotoxic chemotherapy
Decompensated or Child's C cirrhosis
Alfa-fetoprotein (AFP) > 3X ULN (unless negative CT scan or MRI within 3 months of entry date)
Pregnancy or lactation
Any other condition which in the opinion of the investigator might interfere with compliance or outcome of the study

Sites / Locations

HIV-NAT Thai Red Cross AIDS Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Arm Description

AZT+FTC+EFV

TDF+FTC+EFV

Outcomes

Primary Outcome Measures

HBV DNA suppression to levels below the limit of detection (<400 copies/ml)

Secondary Outcome Measures

HBV suppression as measured by comparison of AUC measurements at 12 and 24 weeks

Proportion of patients with undetectable HBV DNA in serum at 12 and 24 weeks

Rate of HBeAg and HBsAg seroconversion at 12, 24 and 48 weeks.

Rate of emergence of LAM-resistant HBV genotypes at 48 weeks.

Rate of hepatic cytolysis (ALT level > 5x ULN).

Change from baseline in ALT levels and time to ALT normalization.

Suppression of plasma HIV-RNA (< 50 copies/ml) through 48 weeks.

Changes in CD4+ /CD8+ cell counts through 48 weeks

Toxicity

Assessment of effect of therapy on histological changes in the liver and effect on ccc-HBV-DNA

Full Information

NCT ID

NCT00476463

First Posted

May 20, 2007

Last Updated

February 18, 2016

Sponsor

The HIV Netherlands Australia Thailand Research Collaboration

Collaborators

Gilead Sciences, Ministry of Health, Thailand

1. Study Identification

Unique Protocol Identification Number

NCT00476463

Brief Title

Efficacy of Tenofovir and Emtricitabine in ARV-naive Patients With HIV/HBV Co-infection

Official Title

Virological and Clinical Anti-HBV Efficacy of Tenofovir and Emtricitabine in Antiretroviral Naive Patients With HIV/HBV Co-infection

Study Type

Interventional

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Completed

Study Start Date

April 2005 (undefined)

Primary Completion Date

December 2008 (Actual)

Study Completion Date

December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The HIV Netherlands Australia Thailand Research Collaboration

Collaborators

Gilead Sciences, Ministry of Health, Thailand

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Combination therapy with anti-HBV activity may both increase HBV suppression rates and reduce emergence of resistant strains. Several new therapeutic agents are currently in development, however combination therapy trials in the HBV-infected population have only recently commenced. No such trials have been undertaken in the HIV/HBV co-infected population.

Detailed Description

The primary study objective is to compare HBV DNA suppression to levels below the limit of detection (<400 copies/ml) by week 48 in each treatment group. Virological and clinical anti-HBV efficacy of tenofovir and emtricitabine in antiretroviral naive patients with HIV/HBV co-infection.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis B Virus, HIV Infections

Keywords

TDF+FTC, FTC, HIV/HBV, TDF compared to TDF+FTC in HIV/HBV, Treatment Naive

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

AZT+FTC+EFV

Arm Title

Arm Type

Active Comparator

Arm Description

TDF+FTC+EFV

Intervention Type

Drug

Intervention Name(s)

Emtricitabine

Intervention Description

Emtricitabine 200 mg OD + Zidovudine 300 mg BID + EFV OD compared to TDF + FTC + EFV

Primary Outcome Measure Information:

Title

HBV DNA suppression to levels below the limit of detection (<400 copies/ml)

Time Frame

week 48

Secondary Outcome Measure Information:

Title

HBV suppression as measured by comparison of AUC measurements at 12 and 24 weeks

Time Frame

12 and 24 weeks

Title

Proportion of patients with undetectable HBV DNA in serum at 12 and 24 weeks

Time Frame

12 and 24 weeks

Title

Rate of HBeAg and HBsAg seroconversion at 12, 24 and 48 weeks.

Time Frame

12, 24 and 48 weeks

Title

Rate of emergence of LAM-resistant HBV genotypes at 48 weeks.

Time Frame

48 weeks

Title

Rate of hepatic cytolysis (ALT level > 5x ULN).

Time Frame

48 weeks

Title

Change from baseline in ALT levels and time to ALT normalization.

Time Frame

48 weeks

Title

Suppression of plasma HIV-RNA (< 50 copies/ml) through 48 weeks.

Time Frame

48 weeks

Title

Changes in CD4+ /CD8+ cell counts through 48 weeks

Time Frame

48 weeks

Title

Toxicity

Time Frame

48 weeks

Title

Assessment of effect of therapy on histological changes in the liver and effect on ccc-HBV-DNA

Time Frame

48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Written informed consent Documented HIV infection (positive serology for HIV-1 and detectable HIV-1 RNA) Age 18 - 70 years HBV DNA > 106 copies/ml HBsAg positive for > 6 months In case documented duration of HBsAg seropositive is less than 6 months (this situation is most likely to occur in patients newly presenting to the HIV-outpatient clinic) the patient is eligible if the patient is: HBsAg positive and HBc core IgM antibody negative and the liver biopsy gives evidence for a chronic active hepatitis. Thus making it likely that this patient has acquired the HBV infection more than 6 months ago. ALT < 10 x ULN Creatinine <= 2.0mg/dl Platelet count >= 50,000/mm3 HIV-1 therapy naive No prior exposure to anti-HBV agents (LAM, adefovir, TDF) although prior IFN treatment allowed Exclusion Criteria: HCV-RNA positive or Anti-HAV IgM positive Acute hepatitis (serum ALT > 1000 U/L) Prior LAM, TDF, or ADV therapy Active opportunistic infection Other causes of chronic liver disease identified ( autoimmune hepatitis, haemochromatosis, Wilsons disease, alfa-1-antitrypsin deficiency) Concurrent malignancy requiring cytotoxic chemotherapy Decompensated or Child's C cirrhosis Alfa-fetoprotein (AFP) > 3X ULN (unless negative CT scan or MRI within 3 months of entry date) Pregnancy or lactation Any other condition which in the opinion of the investigator might interfere with compliance or outcome of the study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kiat Ruxrungtham, MD

Organizational Affiliation

HIV-NAT Thai Red Cross AIDS Research Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

HIV-NAT Thai Red Cross AIDS Research Center

City

Bangkok

ZIP/Postal Code

10330

Country

Thailand

12. IPD Sharing Statement

Links:

URL

http://www.hivnat.org

Description

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)

Learn more about this trial

Efficacy of Tenofovir and Emtricitabine in ARV-naive Patients With HIV/HBV Co-infection

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