Add-on Peginterferon Following Nucleos(t)Ide Analogue Treatment
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|ClinicalTrials.gov Identifier: NCT02364336|
Recruitment Status : Completed
First Posted : February 18, 2015
Results First Posted : August 28, 2019
Last Update Posted : September 4, 2019
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Hepatitis B||Drug: Peginterferon alfa-2a||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||February 14, 2015|
|Actual Primary Completion Date :||May 21, 2018|
|Actual Study Completion Date :||May 21, 2018|
Experimental: HBeAg positive
Patients who have been treated with one or more nucleos(t)ides for at least 192 weeks who have known serum HBsAg and HBeAg positivity
Drug: Peginterferon alfa-2a
Experimental: HBeAg negative
Patients who have been treated with one or more nucleos(t)ides for at least 192 weeks who have known serum HBsAg positivity and HBeAg negativity
Drug: Peginterferon alfa-2a
- Change in Interferon-stimulated-gene (ISG) Expression [ Time Frame: 6 hours after first injection of peginterferon ]Change in level of ISG expression before and after 1st peginterferon injection
- Hepatitis B e Antigen (HBeAg) Loss [ Time Frame: End of treatment, 24 weeks, and 48 weeks ]Proportion of HBeAg positive patients showing eAg loss at end of treatment, and 24 and 48 weeks off peginterferon treatment.
- Hepatitis B s Antigen (HBsAg) Loss [ Time Frame: End of treatment, 24 weeks, and 48 weeks ]Proportion of HBsAg positive patients showing sAG loss at end of treatment and 24 and 48 weeks off peginterferon treatment
- Change in Natural Killer (NK) Cell Frequency [ Time Frame: 6 hours after first injection of peginterferon and baseline ]NK cell frequency is calculated as 100*(NK cells)/(mononuclear cells). Changes are calculated by subtracting baseline from 6 hours after first peginterferon injection.
- Change in Natural Killer (NK) Cell Degranulation [ Time Frame: 6 hours after first injection of peginterferon and baseline ]NK cell degranulation is calculated as 100*(degranulated NK cells)/(NK cells). Changes are calculated by subtracting baseline from 6 hours after first peginterferon injection.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02364336
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Marc G Ghany, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|