Genetic Study of Peginterferon Treatment in Hepatitis B Patients: The GIANT-B Study (GIANT-B)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01401400
Recruitment Status : Completed
First Posted : July 25, 2011
Last Update Posted : August 14, 2015
Information provided by (Responsible Party):
Foundation for Liver Research

Brief Summary:

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

Detailed Description:
For the GWAS stage of this study, a cohort study will be conducted comparing hepatitis B patients with a response (see definitions below) versus patients who did not achieve a response to (peg)interferon treatment. Replication of SNPs identified by the GWAS will be performed in an independent cohort of patients with similar characteristics, treated with (peg)interferon. A large independent cohort of peginterferon treated HBV patients has already been identified guaranteeing a replication cohort.

Study Type : Observational
Actual Enrollment : 1350 participants
Observational Model: Cohort
Time Perspective: Retrospective
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

Resource links provided by the National Library of Medicine

U.S. FDA Resources

(Peg) interferon
Patients who are treated for at least 12 weeks with (peg-)interferon for chronic hepatitis B

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. 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
whole blood samples from which DNA can be isolated

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Chronic hepatitis B patients treated with (peg-)interferon

Inclusion criteria

  • History of chronic hepatitis B, defined as the presence of positive hepatitis B surface antigen (HBsAg) for at least 6 months.
  • History of treatment (per protocol or outside studies) with standard interferon (alfa-2a or alfa-2b), peginterferon alfa-2a or peginterferon alfa-2b for at least 12 weeks.
  • A follow-up duration of at least 24 weeks after the last dose of (peg)interferon.
  • Use of nucleos(t)ide analogues prior to or combined with (peg)interferon treatment is allowed.
  • Available HBV DNA and HBeAg status at baseline, end of treatment and end of follow-up (24 weeks after end of treatment)
  • Written informed consent obtained.

Exclusion criteria

  • Co-infection with hepatitis C virus, delta virus or human immunodeficiency virus.
  • Use of immunosuppressants, chemotherapy or systemic corticosteroids (prednisolone 30 mg daily or equivalent for more than 7 days) during (peg)interferon treatment or the 24-week pre- and post-treatment period.

Information from the National Library of Medicine

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 identifier (NCT number): NCT01401400

Erasmus Medical Centre
Rotterdam, Zuid-Holland, Netherlands, 3015 GE
Sponsors and Collaborators
Foundation for Liver Research
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

Responsible Party: Foundation for Liver Research Identifier: NCT01401400     History of Changes
Other Study ID Numbers: HBV10-03
First Posted: July 25, 2011    Key Record Dates
Last Update Posted: August 14, 2015
Last Verified: August 2015

Additional relevant MeSH terms:
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections