Hepatitis B Immune Globulin (HBIg) to Restore Immune Control in People With Chronic Hepatitis B

Summary

Participation Requirements

Description

Up to 300 subjects with hepatitis B e antigen (HBeAg) negative chronic hepatitis B who are inactive carriers (specified as those with HBV DNA levels <2,000 IU/ml over a 6-month period with ALT levels <1.5 X upper limit of normal and HBsAg level <1500 U/mL) will be screened and 25 enrolled in a rando...

Up to 300 subjects with hepatitis B e antigen (HBeAg) negative chronic hepatitis B who are inactive carriers (specified as those with HBV DNA levels <2,000 IU/ml over a 6-month period with ALT levels <1.5 X upper limit of normal and HBsAg level <1500 U/mL) will be screened and 25 enrolled in a randomized trial of hepatitis B immune globulin (HBIg) for 12 weeks followed by peginterferon alfa for 24 weeks versus peginterferon alfa alone for 24 weeks. The focus of the study is to understand mechanistically what effect the removal of HBsAg will have on the immune response and action of peginterferon alfa-2a. Chronic hepatitis B is characterized by immune exhaustion, which is felt to be caused by ongoing exposure of immune cells to high levels of viral antigens such as HBsAg. Presence of viral antigen results in continuous immune cell stimulation leading to functional exhaustion and progressive loss of immune function. In this study, we will attempt to achieve elimination of circulating HBsAg from the blood of chronically infected patients by administering high doses of hepatitis B immunoglobulin followed by peginterferon. A control arm consisting of peginterferon alone will be included to allow for assessment of the effect of HBIg on response to peginterferon alfa-2a. We will investigate whether this strategy will result in restoration of and/or increase in innate immunity leading to HBsAg clearance and development of long-lasting protective immunity. The proposed study will be conducted in three phases with pre-specified stopping rules to ensure subjects are responding appropriately at the end of each phase before moving to the next phase. The primary endpoints of the trial will be restoration of HBV-specific adaptive immunity at two time points (the end of HBIg treatment (week 12) and at the end of treatment (week 36) and increase in innate immune response to peginterferon alfa-2a treatment and a secondary endpoint will be a greater than 0.5 log10 reduction in HBsAg level at the study end point (week 36).

Tracking Information