Chronic Hepatitis B Clinical Trial
Official title:
Mechanisms Associated With Favorable Response to Peginterferon-Alpha Add-on Therapy Following Long-term Nucleos(t)Ide Analogue Treatment in Patients With Chronic Hepatitis B
Background:
- Chronic hepatitis B is caused by a virus that infects the liver. Cure is not possible but
the virus can be controlled with the use of antiviral medicines,. Researchers think that
adding a second antiviral medicine might help.
Objective:
- To understand how peginterferon might help treat people with chronic hepatitis B. Also, to
see if peginterferon is safe to use with other antiviral medications.
Eligibility:
- Adults age 18 and older who have chronic hepatitis B and had therapy with 1 or more oral
medicines for hepatitis B for at least 4 years.
Design:
- Participants will be screened with physical exam and medical history. They will complete
health questionnaires about their levels of fatigue and pain. They will have blood and
urine tests. They may have an eye exam.
- Participants also will have a Fibroscan. A test to measure how stiff your liver is.
- Eligible participants will have a liver biopsy. Blood will be drawn.
- Participants will be admitted to the NIH Clinical Center. They will be injected with the
study drug. Then they will have a second liver biopsy. They will be discharged 24 hours
later.
- Participants will give themselves study drug injections under the skin weekly for 24
weeks.
- Participants will have 5 clinic visits during the 24-week treatment period. Then they
will have follow-up visits every 12 weeks for 48 weeks.
- During visits, participants may have a physical exam and medical history. They may have
blood and urine tests. They may have a Fibroscan and complete questionnaires. At the
final visit, they will also have a Fibroscan.
Chronic hepatitis B virus (HBV) infection is a leading cause of liver associated morbidity
and mortality. Currently available first-line therapies for treatment of chronic hepatitis B
include pegylated interferon-alpha and the nucleos(t)ide analogues (NUCs) entecavir and
tenofovir. These were shown to effectively suppress viral replication, but their ability to
induce durable off-treatment response is limited to a small subset of patients. Combination
treatment with peginterferon and NUCs has been attempted in several randomized controlled
trials, with no apparent advantage over either agent given alone. In these studies however,
treatment with peginterferon was initiated either simultaneously or shortly after NUCs
administration. The efficacy of peginterferon following long-term viral suppression with NUCs
was only tested in one small pilot study, nevertheless showing 60% hepatitis B s antigen
(HBsAg) loss rate.
The underlying mechanisms responsible for improved efficacy of peginterferon in this setting
are unknown and warrant further investigation. In this single arm study we propose to
evaluate the efficacy and mechanisms associated with response to peginterferon add-on therapy
following a minimum of 192 weeks of viral suppression induced by NUCs in a group of chronic
HBV infected patients. Sixty patients with either hepatitis B e antigen (HBeAg) positive
(n=30) or negative (n=30) chronic HBV infection will be enrolled to this study. After medical
evaluation and pretreatment liver biopsy, treatment with subcutaneous injections of pegylated
interferon alpha-2a 180 g per week will be given for a total of 24 weeks, followed by an
off-treatment evaluation period of 48 weeks. A second liver biopsy will be performed six
hours following the first peginterferon injection. Primary end-point for this study will be
the change in interferon-stimulated-genes response before and after first interferon
injection in responders versus non-responders to treatment. The responsiveness to IFN-based
therapy of treatment responders vs nonresponders will additionally be evaluated by studying
intrahepatic and peripheral blood natural killer cells. The study will also assess HBeAg and
HBsAg loss and seroconversion rates in comparison to historical controls treated with either
peginterferon or NUCs monotherapy. Finally, we will assess whether treatment responders
develop an HBV-specific T cell response similar in quantity and quality to that of patients
who spontaneously resolve HBV infection.
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