A Comparison of Adefovir and Tenofovir for the Treatment of Lamivudine-Resistant Hepatitis B Virus in People With HIV
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections; Hepatitis B
Intervention: Adefovir dipivoxil (Drug); Tenofovir disoproxil fumarate (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s): Bruce Polsky, MD, Study Chair, Affiliation: St. Luke's-Roosevelt Hospital Center Marion Peters, MD, Study Chair, Affiliation: University of California, San Francisco
Summary
Control of hepatitis B virus (HBV) infection can be difficult in HIV infected people who
have taken the antiviral lamivudine (3TC). These people may have HBV that has become
resistant to 3TC. Adefovir dipivoxil (ADV) has shown promising anti-HBV activity in clinical
trials; tenofovir disoproxil fumarate (TDF) is used to treat HIV and may also be effective
against HBV. The purpose of this study is to find out if adding ADV or TDF to a highly
active antiretroviral therapy (HAART) regimen that includes 3TC has an effect on HBV
infection in patients coinfected with HIV and HBV. The tolerability and safety of these
drugs will be examined.
Clinical Details
Official title: A Randomized, Phase II, Controlled Trial Comparing the Efficacy of Adefovir Dipivoxil and Tenofovir Disoproxil Fumarate for the Treatment of Lamivudine-Resistant Hepatitis B Virus in Subjects Who Are Co-Infected With HIV
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment
Detailed description:
HBV presents a worldwide health crisis and is difficult to treat when a patient's HBV strain
is no longer responsive to 3TC. Given the significant incidence of 3TC-resistant HBV in
patients receiving this drug as part of an antiretroviral regimen, other agents with
anti-HBV activity are needed. ADV has shown promising anti-HBV activity in preclinical
assessments and in Phase I, II, and III clinical trials. TDF, developed for the treatment of
HIV infection, has in vitro activity against HBV. This study will compare TDF/3TC
combination therapy with ADV/3TC combination therapy to determine which treatment regimen is
more effective in patients coinfected with HBV and HIV.
This study will include two populations of patients. Patients in Population A are on stable
HAART that includes TDF and will either be in Group I (compensated liver disease) or Group
II (decompensated liver disease). All patients in Population A will be randomly assigned to
one of two arms: Arm 1 patients will receive 10 mg ADV daily and TDF placebo; Arm 2 patients
will receive ADV placebo and 300 mg TDF. Patients in Population B are on stable HAART and
have never taken TDF as part of their HAART. Population B patients will receive 300 mg TDF
daily during the course of the study.
Study visits will occur every 4 weeks for the 96-week study period. Targeted clinical and
medication assessments and blood work assessing clotting time, liver function, and blood
chemistry will be conducted at each study visit. HIV and HBV DNA viral load will be tested
every 12 weeks. CD4 cell counts will be tested at Weeks 24, 48, 72, and 96.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria for All Participants:
- HIV infected
- HBV infected
- Serum HBV DNA of 100,000 copies/ml or greater
- Positive for serum hepatitis B surface antigen (HBsAg) within 12 weeks prior to study
entry
- Agree to use acceptable methods of contraception
- Serum alpha-fetoprotein (AFP) of 50 ng/ml or less within 30 days of study entry. If
AFP is greater than 50 ng/ml, the patient must have an imaging study of the liver
showing no tumor within 30 days prior to study entry
Inclusion Criteria for Population A:
- Uninterrupted stable HAART regimen at study entry for at least 12 continuous weeks
prior to study entry
- HIV viral load of 10,000 copies/ml or less within 12 weeks of study entry
Inclusion Criteria for Population A, Group I:
- Compensated liver disease
- Child-Pugh-Turcotte (CPT) score of less than 7
Exclusion Criteria for Population A, Group I:
- Excess fluid in the space between the membranes lining the abdomen and abdominal
organs (ascites)
- Gastrointestinal (variceal) bleeding
- Brain and nervous system damage as a result of liver disease
- Abnormal blood clotting time
Inclusion Criteria for Population A, Group II:
- Decompensated liver disease
- CPT score of 7-12
Inclusion Criteria for Population B:
- Prior HAART regimen
- Never taken TDF as part of HAART regimen
- Serum HBV DNA of 100,000 copies/ml or greater within 12 weeks of study entry
- HIV viral load of greater than 10,000 copies/ml within 12 weeks of study entry
- CPT score less than 13
Exclusion Criteria
- Serious kidney problems within the last 12 months
- Allergic or sensitive to ADV or TDF
- Active hepatitis C virus (HCV) disease or unknown HCV status within 24 weeks of study
entry
- Any medical or mental illness that, in the opinion of the investigator, would
interfere with the protocol
- Past or current alcohol or drug abuse that would affect the protocol
- Malignancy that, in the opinion of the investigator, would make the patient
unsuitable for the study
- Certain anti-HBV drugs within 90 days of study entry or expected use of these agents
during the course of the study
- Drugs that may damage the kidneys within 8 weeks prior to study screening or expected
use of these agents during the course of the study
- Systemic corticosteroids within 90 days of study entry
- Current use of drugs containing pivalic acid
- Certain investigational anti-HIV agents
- Pregnant or breastfeeding
Locations and Contacts
UC Davis Medical Center, Sacramento, California 95814, United States
Univ. of California Davis Med. Ctr., ACTU, Sacramento, California, United States
Ucsf Aids Crs, San Francisco, California 94110, United States
University of Colorado Hospital CRS, Aurora, Colorado 80262, United States
Cook County Hosp. CORE Ctr., Chicago, Illinois 60612, United States
Northwestern University CRS, Chicago, Illinois 60611, United States
Johns Hopkins Adult AIDS CRS, Baltimore, Maryland 21287, United States
Beth Israel Med. Ctr., ACTU, New York, New York 10003, United States
Cornell CRS, New York, New York 10021, United States
NY Univ. HIV/AIDS CRS, New York, New York 10016, United States
Weill Med. College of Cornell Univ., The Cornell CTU, New York, New York, United States
Univ. of Cincinnati CRS, Cincinnati, Ohio 452670405, United States
MetroHealth CRS, Cleveland, Ohio 441091998, United States
Vanderbilt Therapeutics CRS, Nashville, Tennessee 37203, United States
University of Washington AIDS CRS, Seattle, Washington 98104, United States
Additional Information
Click here for more information about tenofovir disoproxil fumarate Haga clic aquí para ver información sobre este ensayo clínico en español.
Related publications: Benhamou Y, Bochet M, Thibault V, Di Martino V, Caumes E, Bricaire F, Opolon P, Katlama C, Poynard T. Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients. Hepatology. 1999 Nov;30(5):1302-6. Benhamou Y, Bochet M, Thibault V, Calvez V, Fievet MH, Vig P, Gibbs CS, Brosgart C, Fry J, Namini H, Katlama C, Poynard T. Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study. Lancet. 2001 Sep 1;358(9283):718-23. Dieterich DT. HIV and hepatitis B virus: options for managing coinfection. Top HIV Med. 2003 Jan-Feb;11(1):16-9. Review. Rockstroh JK. Management of hepatitis B and C in HIV co-infected patients. J Acquir Immune Defic Syndr. 2003 Sep;34 Suppl 1:S59-65. Review. Thio CL. Hepatitis B in the human immunodeficiency virus-infected patient: epidemiology, natural history, and treatment. Semin Liver Dis. 2003 May;23(2):125-36. Review.
Last updated: May 17, 2012
|