Mechanisms Associated With Favorable Responses to Peginterferon-Alpha Add-on Therapy Following Long-term Nucleos(t)Ide Analogue Treatment in Patients With Chronic Hepatitis B
- 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.
- 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.
- 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.
- 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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Change in interferon-stimulated-genes [ Time Frame: Week 4 of Therapy ] [ Designated as safety issue: No ]
- HBeAg and HBsAg seroconversion [ Time Frame: 24 & 48 weeks off ] [ Designated as safety issue: No ]
|Study Start Date:||February 2015|
|Estimated Study Completion Date:||September 2017|
|Estimated Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
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% 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 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02364336
|Contact: Nancy Fryzek||(301) firstname.lastname@example.org|
|Contact: Marc G Ghany, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Marc G Ghany, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|