Genetic Study of Peginterferon Treatment in Hepatitis B Patients: The GIANT-B Study (GIANT-B)
|ClinicalTrials.gov Identifier: NCT01401400|
Recruitment Status : Completed
First Posted : July 25, 2011
Last Update Posted : August 14, 2015
Background and rationale Chronic hepatitis B is the most common cause of liver cirrhosis and hepatocellular carcinoma worldwide.(1) Antiviral therapy with oral nucleoside analogs and interferon can reduce viral load and hepatic necroinflammation, and may reduce the risk of hepatocellular carcinoma and cirrhotic complications. (2-4) Peginterferon has both direct antiviral and immunomodulatory effects. The advantages of this drug include a finite course of treatment and the lack of drug resistance. However, it requires subcutaneous injections and carries some side effects. Besides, only 30% to 40% of treated patients have sustained response to treatment.(5-8) To reduce the costs and side effects of treatment, it is important to predict if a patient will respond to peginterferon. Genetic host studies on peginterferon response will provide a lot of knowledge on the interaction between the host and the virus to induce immune control, also outside the setting of immune modifying therapy. Recently, genome wide association studies (GWAS) identified genetic polymorphisms of the IL28B gene that were shown to be associated with treatment response to interferon and ribavirin in patients with chronic hepatitis C.(9-12) The same polymorphisms are also associated with natural clearance of hepatitis C virus. Whether the same phenomenon applies to patients with chronic hepatitis B is unclear. Furthermore, response to conventional interferon has shown to decrease the risk of hepatocellular carcinoma and to prolong survival.(13) Virological and serological response to PEG-IFN is durable in a substantial proportion of patients through 3 years of follow-up (14), but whether treatment benefits are sustained after that period and amount to clinically meaningful results is unknown. To date, a GWAS to predict the response to peginterferon in chronic hepatitis B patients has not been performed. Polymorphisms in genes such as IL28B can be identified through a GWAS and can be used to assess the chance of response to treatment and select patients who have a high probability of response to peginterferon.
We aim to perform a GWAS in chronic hepatitis B patients previously treated with peginterferon to identify polymorphisms in genes that are associated with response to this treatment regimen.
|Condition or disease|
|Chronic Hepatitis B|
|Study Type :||Observational|
|Actual Enrollment :||1350 participants|
|Official Title:||Genetic Study of Peginterferon Treatment in Hepatitis B Patients: The GIANT-B Study|
|Study Start Date :||May 2010|
|Actual Primary Completion Date :||June 2015|
|Actual Study Completion Date :||June 2015|
Patients who are treated for at least 12 weeks with (peg-)interferon for chronic hepatitis B
- Response to (PEG)IFN in relation to single-nucleotide polymorphisms identified by a GWAS [ Time Frame: 24 weeks off-treatment ]
HBeAg-positive patients: HBV DNA <2000IU/ml and HBeAg seroconversion; 24 weeks off-treatment.
HBeAg-negative patients: HBV DNA <2000IU/ml
- Response [ Time Frame: 24 weeks off-treatment ]HBV DNA <20IU/ml for both HBeAg positives as negatives sustainability of HBeAg seroconversion or HBeAg loss(only HBeAg+ patients) HBsAg loss and seroconversion, ALT normalization, data on survival, incidence of cirrhosis, hepatocellular carcinoma and liver transplantation.
Biospecimen Retention: Samples With DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01401400
|Erasmus Medical Centre|
|Rotterdam, Zuid-Holland, Netherlands, 3015 GE|
|Principal Investigator:||Harry LA Janssen, MD PhD||Foundation of Liver research (SLO), Rotterdam AND UHN liver clininc, Toronto Western & General Hospital|
|Study Chair:||Pietro Lampertico, MD PhD||IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Milan|
|Study Chair:||Henry Chan, MD||The Chinese University of Hong Kong, Department of Medicine and Therapeutics|
|Study Chair:||Jin-Lin Hou, MD PhD||Nanfang Hospital, Southern Medical University, Hepatology Unit and Dept of Infectious Diseases|