Lamivudine and Adefovir to Treat Chronic Hepatitis B Infection in People With and Without HIV Infection
This study will evaluate the safety and effectiveness of adefovir plus lamivudine for chronic hepatitis B infection in people with and without HIV infection. Lamuvidine, an FDA-approved treatment for hepatitis B infection, also works against HIV. In some patients, the hepatitis B virus (HBV) continues to reproduce despite lamivudine treatment. Adefovir is an experimental drug that inhibits HBV replication and may work against some strains of the virus that have become resistant to lamivudine.
Patients 21 years of age or older with active hepatitis B infection despite treatment with lamivudine for at least 1 year may be eligible for this 48-week study. Patients both with or without HIV infection may participate. Candidates will be screened with a medical history, blood and urine tests, liver ultrasound exam, electrocardiogram (EKG) and chest X-ray.
Participants will have a physical examination, review of their medical history, blood tests, and a 24-hour urine collection. They will be admitted to the hospital for a liver biopsy to determine if they can receive the study drug. For this procedure, the patient is given a sedative for relaxation. The skin over the biopsy is numbed with an anesthetic and the biopsy needle is passed rapidly into and out of the liver to collect a tissue specimen. Patients are monitored in the hospital overnight for possible complications. After discharge, they return home and begin taking the study medications.
Patients will be randomized to two treatment groups. One group will take 10 milligrams/day of adefovir by mouth, and the other will take a placebo-a lookalike pill with no active ingredient. Both groups will also take 150 mg lamivudine by mouth and L-carnitine pills or liquid. Patients with HIV infection will continue to take antiretroviral therapy as well.
Patients will be followed in the clinic at study weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44 for blood and urine tests to determine the safety of the drug and to evaluate the response to treatment. On week 48, a repeat 24-hour urine test and repeat liver biopsy will be done. At the end of the 48 weeks, patients may continue to receive adefovir for another 48 weeks and possibly longer. All those who participate in this extension phase will receive active adefovir, regardless of whether they had previously taken adefovir or placebo.
All patients will have the option to enroll in a separate study to examine the levels of HBV (and levels of HIV in HIV-infected patients) in the blood immediately after starting treatment and to determine if these initial levels can predict later outcome. This involves seven additional visits, for which participants will be compensated. At these visits, blood will be drawn on study days 0 (before starting drug treatment), 1, 3, 5, 7, 10 and 21 for HIV and HBV viral loads and specialized immunology tests.
|Study Design:||Endpoint Classification: Efficacy Study
Primary Purpose: Treatment
|Official Title:||Studies of the Addition of Adefovir Dipivoxil to Lamivudine for the Treatment of Chronic Hepatitis B: A Randomized, Double-Blind, Placebo Controlled Study in HIV-Infected Patients and an Open-Label Study in HIV-Negative Subjects|
|Study Start Date:||August 2001|
|Estimated Study Completion Date:||October 2004|
This clinical trial examines the addition of adefovir dipivoxil to a lamivudine regimen for treating chronic hepatitis B infection. Two patient populations will be separately recruited: HIV-infected (40 subjects) and HIV-uninfected (20 subjects). HIV-infected patients will be enrolled in a randomized, placebo controlled study of the safety and efficacy of the addition of adefovir to lamivudine for the treatment of chronic hepatitis B in subjects with a hepatitis B virus (HBV) viral load of at least one million copies/mL despite at least one year of lamivudine therapy. A similar population of HIV-uninfected subjects will be treated with open-label adefovir 10 mg daily for one year. These HIV-negative subjects will serve as a control group for immunological comparisons to the HIV-positive group treated with adefovir. HIV-infected subjects will be randomly allocated to receive adefovir 10 mg daily for one year or matching placebo. At the end of one year, HIV-infected patients may choose to receive open-label adefovir, and HIV-uninfected patients will have the option of continuing open-label drug if they are responding to treatment. Patients may not have decompensated cirrhosis or other causes of liver disease such as hepatitis C. Liver biopsies are performed prior to study and at the end of one year. HIV-positive subjects whose liver biopsy demonstrates cirrhosis will not be randomized but will be treated with open-label adefovir 10 mg daily. The purpose of the study is to evaluate the safety and efficacy of lamivudine plus adefovir as compared with continued lamivudine in HIV-infected patients, to compare responses between HIV-uninfected and HIV-infected subjects, and to obtain specimens for studies of immune responses to HBV. HIV-infected patients will receive lamivudine 150 mg bid plus adefovir 10 mg qd (or placebo) and HIV-uninfected subjects will receive lamivudine 100 mg qd plus adefovir 10 mg qd. L-carnitine supplementation will be used only if low serum carnitine levels are documented. Additionally, patients will have the option of enrolling in a sub-study assessing the kinetics of viral load response to study drug. Specimens will be stored for possible future determination of adefovir levels and use in evaluating HBV and HIV resistance to adefovir. Patients discontinuing study drug and not initiating a commerically available anti-HBV medication (including adefovir) will be monitored for safety for at least an additional 24 weeks. The primary study endpoint will be a comparison of the absolute HBV viral load at Week 48 between the placebo and adefovir HIV-positive patient groups, and for the HIV-negative population, the comparison of absolute HBV viral at Week 48 versus baseline. Secondary endpoints include safety, liver pathology, and transaminase level. Adefovir will be discontinued for toxicity; there will be no dose reduction. A DSMB will oversee the trial for toxicity.
|United States, Maryland|
|National Institute of Allergy and Infectious Diseases (NIAID)|
|Bethesda, Maryland, United States, 20892|