Study Comparing the Safety of Switching From Lamivudine to Adefovir Dipivoxil Versus Overlapping Lamivudine and Adefovir Before Adefovir Dipivoxil Monotherapy in Patients With Chronic Hepatitis B



Status:Recruiting
Conditions:Hepatitis
Therapuetic Areas:Immunology / Infectious Diseases
Healthy:No
Age Range:18 - Any
Updated:3/30/2013
Start Date:May 2005
Contact:Meejin Ahn, BS
Email:mxa001@jefferson.edu
Phone:215-955-5806

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A Single Center Open-Label, Randomized Study Comparing the Safety of Immediately Switching From Lamivudine to Adefovir Dipivoxil Versus Overlapping Lamivudine and Adefovir for 12 Weeks Before Instituting Adefovir Dipivoxil Monotherapy in Patients With Chronic Hepatitis B


In earlier clinical studies, when patients who have been on lamivudine (LAM) were switched
to adefovir dipivoxil (ADV), some patients developed ALT flares with an elevation of ALT >
10 x the upper limits of normal (ULN).

There were no cases of hepatic decompensation with the flares, however. The transition
methods were varied among physicians from no overlapping to overlapping for 1 to 3 months
with LAM and ADV. There is still some uncertainty about the optimal approach to switching
from LAM to ADV.

This study will compare the safety of directly switching to ADV to a protocolled switch
after a period of overlap of 12 weeks. This will facilitate pro-active switching in
patients on LAM and will also highlight genotypic resistance ahead of phenotypic resistance
as a reason to switch patients. Data to date have only been presented as part of a
controlled study in patients with clinically evident LAM-resistance. This study will enroll
patients who still have serum hepatitis B virus (HBV) DNA suppression whilst receiving LAM.


Chronic HBV infection is an important worldwide cause of morbidity, mortality and source of
potential new infections. There are an estimated 350 million carriers of HBV in the world.
In China, Southeast Asia and sub-Saharan Africa, as many as 10-15% of the population are
chronically infected. In North America and Northern Europe, infection and carrier rates are
much lower, usually below 1%. Intermediate carrier rates of 1-5% are found in Southern
Europe (e.g., Italy, Greece and Spain), parts of South and Central America, the Middle East
and Japan. Persistent infection develops in over 90% of perinatally infected children and
in 3-10% of people who become infected after the age of 6 years. Worldwide, it has been
estimated that more than one million people die annually due to HBV-related end stage
diseases such as cirrhosis and hepatocellular carcinoma.

The goal of antiviral therapy for hepatitis B is to reduce a patient’s risks for progressive
liver disease through prolonged suppression or eradication of HBV infection and to arrest or
ameliorate HBV-related liver damage.

Inclusion Criteria:

- Males and females ≥ 18 years of age with chronic hepatitis B

- Hepatitis B surface antigen (HBsAg)(+) for a minimum of 6 months prior to entry

- Hepatitis B envelope antigen (HBeAg)(+) or (-) at baseline

- Patients having previously received LAM for at least 24 weeks

- Patients with compensated liver function (Child-Pugh score ≤ 6)

Exclusion Criteria:

- Any serious or active medical or psychiatric illness which, in the opinion of the
investigator, would interfere with patient treatment, assessment or compliance with
the protocol.

- Received immunoglobulins, interferon or other immune or cytokine-based therapies with
possible activity in hepatitis B disease within 6 months prior to study screening.

- Organ or bone marrow transplant recipients.

- Evidence of active liver disease due to other causes (e.g., Wilson’s disease,
hemochromatosis, autoimmune hepatitis, hepatitis C or hepatitis D co-infection)

- Patients taking parenteral (intravenous or intramuscular or subcutaneous) or oral
steroids, immuno-suppressant therapies or chemotherapeutic agents within 2 months of
study screening or expected to receive these agents during the course of the study.

- Previous participation in an investigational trial involving administration of any
investigational compound within 2 months prior to the study screening or those who
received anti-HBV therapy other than lamivudine within the previous 3 months (e.g.
anabolic steroids, ketaconazole, itraconazole, isoniazid, rifampin, rifabutin,
simvastatin, lovastatin)

- Clinically relevant alcohol or drug use or history of alcohol or drug use considered
by the investigator to be sufficient to hinder compliance with treatment, follow up
procedures or evaluation of adverse events

- Lactating females or females with a positive serum pregnancy test.

- Females of childbearing potential (post-puberty) unwilling or unable to have
pregnancy testing at any study visit

- Therapy with nephrotoxic drugs (e.g. aminoglycosides, amphotericin B, vancomycin,
cidofovir, foscarnet, cisplatin pentamidine, tacrolimus, cyclosporine) or competitors
of renal excretion (e.g. probenecid) within 2 months prior to study screening or the
expectation that subject will receive these during the course of the study.

- The use of antiviral therapy with agents demonstrating potential anti-HBV activity
other than lamivudine within the previous 3 months (e.g. famciclovir, lobucavir,
emtricitabine, DAPD, L-FMAU, entecavir, ganciclovir or others).

- History of hypersensitivity to nucleoside and/or nucleotide analogues.

- Clinical, ultrasonographic or radiologic evidence of hepatic mass suggestive of
hepatocellular carcinoma.

- Serum alphafetoprotein (AFP) > 50 ng/mL at the first screening visit. However, if the
AFP level is > 50 ng/mL at the first screening visit, but has remained stable or
decreased over the 6 months preceding the first screening visit, and if there is no
radiologic or ultrasonic evidence of hepatic mass(es) suggestive of hepatocellular
carcinoma, the patient will be allowed to enroll.

- Inability to comply with study requirements.
We found this trial at
1
site
111 S 11th St
Philadelphia, Pennsylvania 19107
(215) 955-6000
Thomas Jefferson University Hospital Our hospitals in Center City Philadelphia share a 13-acre campus with...
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Philadelphia, PA
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