NCT03575208

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

Use of Hepatitis B Immune Globulin (HBIg) to Restore Immune Control in Patients With Chronic Hepatitis B

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Background: Hepatitis B is a viral infection of the liver. When the immune system tries to clear hepatitis B, it damages the liver. Eventually, the immune system gets exhausted fighting the virus. Researchers want to see if giving large doses of an antibody (HBIg) with the drug peginterferon will boost the immune system in people with this disease. Objectives: To observe the effect of large doses of antibody against the hepatitis B surface antigen on the immune response to the virus. To see if removing hepatitis B surface antigen from the blood enhances the action of peginterferon. Eligibility: Adults ages 18 and older with hepatitis B Design: Participants will be screened twice with a medical history, physical exam, and blood and urine tests. Participants will be randomly put in one of two groups. All participants will get peginterferon for 24 weeks. One group will first get HBIg for 12 weeks. Participants in the combination group will have a 4-day clinic stay. They will have: Repeats of screening tests Eye exam Liver ultrasound The first dose of HBIg by IV over 2 hours These participants will get HBIg at the clinic up to 8 times over 12 weeks then start the peginterferon. All participants will get peginterferon for 24 weeks. They will get it by injection under the skin once a week. They may do this themselves. They will keep a drug diary. They will have 5 visits to assess response and monitoring for safety.. After stopping the study drug, participants will have 4 follow-up visits over 36 weeks. They will repeat screening tests and have 1 liver ultrasound.

Detailed 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 IU/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-2a 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 alfa-2a. A control arm consisting of peginterferon alfa-2a 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).

Conditions

• Chronic Hepatitis B

Interventions

Type	Name	Description
BIOLOGICAL	hepatitis B immune globulin (HBIg)	HBIg 20,000 U/L iv. Dosing interval will depend on anti-HBs levels.
DRUG	Pegylated interferon alfa (pegIFN)	peginterferon alfa-2a 180 mcg weekly for 24 weeks

Timeline

• Start date: 2019-02-13
• Primary completion: 2022-03-29
• Completion: 2022-03-29
• First posted: 2018-07-02
• Last updated: 2022-04-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study