Long-Term Lamivudine Therapy for Chronic Hepatitis B


Phase 4
18 Years
N/A
Not Enrolling
Both
Hepatitis B, Chronic

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Trial Information

Long-Term Lamivudine Therapy for Chronic Hepatitis B


The major aims of this study are to evaluate the long-term efficacy and safety of lamivudine
therapy and the possibility of stopping therapy in a cohort of patients with chronic
hepatitis B who have a maintained response to treatment. Lamivudine is a nucleoside
analogue with potent activity against hepatitis B virus (HBV), which is approved for use in
the United States and is used extensively throughout the world to treat HBV and HIV
infection. Lamivudine is well tolerated and adverse events are rare. Its major shortcoming
is the development of antiviral resistance after prolonged therapy which results in loss of
effectiveness, marked by rise in viral levels and return of disease activity. Some
patients, however, have a maintained response to lamivudine therapy and in these individuals
treatment is continued indefinitely or until hepatitis B surface antigen (HBsAg) is lost and
therapy can be permanently stopped. This protocol will allow for the long-term treatment
and evaluation of these patients. Patients will be maintained on lamivudine at a dose of
100 mg daily and seen every three months for interim medical history and serum testing for
aminotransferase levels and hepatitis B markers, with liver biopsies done every 5 years.
Lamivudine will be stopped if HBsAg is lost. The protocol also includes an option to attempt
withdrawal of therapy under controlled conditions focusing on inducing immune reactivity to
HBV and clearance of HBsAg. Patients will stop lamivudine for short periods (1 week, and
later for 2, 4 and 8 weeks) and be monitored during and for 12 weeks afterwards for
aminotransferase levels, HBV DNA levels and CD4+ and CD8+ T cell responses to HBV antigens.
Patients who demonstrate significant worsening of hepatitis will not undergo further
attempts at withdrawal. The endpoint to successful therapy is defined as loss of hepatitis B
surface antigen (HBsAg) and development of antibody (anti-HBs).

Inclusion Criteria


- INCLUSION CRITERIA:

- Age 18 years or above, male or female

- Presence of HBsAg in serum for at least 6 months.

- Previous liver biopsy histology showing chronic hepatitis with or without cirrhosis.

- Long-term (greater than 1 year) lamivudine therapy in doses of 100 mg daily.

- Normal or near normal (less than twice the upper limit of normal) serum
aminotransferase levels.

- HBV DNA levels below 10(5) copies per ml while on lamivudine.

- Written informed consent.

EXCLUSION CRITERIA:

- In women, pregnancy, breast feeding, and, in those capable of bearing children,
inability to practice adequate contraception.

- Significant systemic illnesses other than liver disease, including congestive heart
failure, renal failure, chronic pancreatitis, or diabetes mellitus with poor control.

- Serum creatinine greater than 1.5 mg/dL and creatinine clearance less than 50 cc/min.

- A history of clinically apparent pancreatitis or evidence of subclinical pancreatitis
as shown by serum amylase values twice the upper limits of the normal range and
abnormalities of the pancreas on computerized tomography or other imaging studies of
the abdomen.

- Severe cirrhosis as defined by Child's stage C (Child-Pugh score of 7 or above).

- HIV infection as indicated by presence of anti-HIV in serum.

- Chronic hepatitis C as shown by the presence of anti-HCV and HCV RNA in serum.

- Immunosuppressive therapy requiring use of more than 10 mg of prednisone (or its
equivalent) per day.

- Other antiviral therapy for chronic hepatitis B within the previous 3 months.

- Sensory or motor neuropathy apparent from medical history and physical examination.

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Authority:

United States: Federal Government

Study ID:

050195

NCT ID:

NCT00120354

Start Date:

July 2005

Completion Date:

March 2007

Related Keywords:

  • Hepatitis B, Chronic
  • Hepatitis B Virus
  • Antiviral Resistance
  • Drug Withdrawal
  • Immune Response
  • Hepatitis B Surface Antigen
  • Liver Biopsy
  • Hepatitis B
  • Hepatitis
  • Hepatitis A
  • Hepatitis B
  • Hepatitis, Chronic
  • Hepatitis B, Chronic

Name

Location
National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892