- ICH GCP
- US Clinical Trials Registry
- Clinical Trial 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
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Maryland
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Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
- INCLUSION CRITERIA:
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Male or female >=18 years of age
- Known serum HBsAg positive with a level <1,500 IU/mL measured within 144 weeks of screening
- Hepatitis B e antigen negative at the time of screening
- HBV DNA levels <2000 IU/mL measured on two occasions at least 24 weeks and no more than 48 weeks apart, during screening
- ALT level <=1.5 ULN measured on two occasions at least 24 weeks and no more than 48 weeks apart, during screening
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
- Any treatment for HBV within the last 48 weeks
- Co-infection with HDV as defined by the presence of anti-HDV
- Co-infection with HCV as defined by the presence of anti-HCV with HCV RNA
- Co-infection with HIV as defined by the presence of anti-HIV
- Presence of anti-HBs
- Cirrhosis either diagnosed by a prior liver biopsy at any time or if not available by a transient elastography score >13 kPa.
- Decompensated liver disease as defined by serum bilirubin >2.5 mg/dL (with direct bilirubin > 0.5 mg/dL), prothrombin time of greater than 2 seconds prolonged, a serum albumin of less than 3.5 g/dL, or a history of ascites, variceal bleeding or hepatic encephalopathy.
- Presence of other causes of liver disease, (i.e. hemochromatosis, Wilson disease, alcoholic liver disease, alpha-1-anti-trypsin deficiency).
- A history of organ transplantation, or in the absence of organ transplantation any medical condition requiring the chronic use of more than 5 mg of prednisone (or its equivalent) daily.
- Severe IgA deficiency
- Severe allergic reaction to any human immunoglobulin product
- Significant systemic illness other than liver diseases including congestive heart failure, renal failure, chronic pancreatitis, and diabetes mellitus with poor control, that in the opinion of the investigator may interfere with therapy.
- Pregnancy or for women of childbearing potential, inability or unwillingness to use an effective form of contraception during study participation.
- Lactating women.
- Hepatocellular carcinoma (HCC), or the presence of a mass on imaging studies of the liver that is suggestive of HCC, or an alpha-fetoprotein level of greater than 500 ng/mL
- eGFR < 50 ml/min, serum creatinine > 1.3 mg/dL
- History of hypersensitivity to pegylated interferon-alpha
- Platelet count <90 mm3/dL
- Hgb <12 g/dL for males and <11 g/dL for females
- Active ethanol/drug abuse/psychiatric problems such as major depression, schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety, or personality disorder that, in the investigator s opinion, might interfere with participation in the study.
- History of malignancy or treatment for a malignancy within the past 3 years (except adequately treated carcinoma in situ or basal cell carcinoma of the skin).
- History of immune-mediated disease, or cerebrovascular, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by a study physician.
- Presence of conditions that, in the opinion of the investigators, would not allow the patient to be followed in the current study.
- Inability of subject to understand and the unwillingness to sign a written informed consent document.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: HBIG followed by Peginterferon alfa-2a
HBIg x 12 weeks followed by peginterferon alfa-2a 180mcg x 24 weeks
|
HBIg 20,000 U/L iv.
Dosing interval will depend on anti-HBs levels.
peginterferon alfa-2a 180 mcg weekly for 24 weeks
|
Active Comparator: Peginterferon alfa-2a
Peginterferon alfa-2a 180mcg x 24 weeks
|
peginterferon alfa-2a 180 mcg weekly for 24 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
NK cell response to the first peginterferon injection both groups
Time Frame: 6 hours after the first peginterferon injection
|
Change in TRAIL-expressing NK cell within the first 6 hours after the first peginterferon injection
|
6 hours after the first peginterferon injection
|
Improvement of HBsAg-specific T cell responses HBIG only group
Time Frame: Baseline to week 12
|
Change in the frequency of IFN-g producing T cells from baseline to week 12 as compared to HBV core and polymerase-specific T cell responses in the same patients
|
Baseline to week 12
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Improvement of HBsAg-specific T cell responses both groups
Time Frame: Baseline to week 36
|
Change in the frequency of IFN-g producing T cells from baseline to week 36
|
Baseline to week 36
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HBsAg loss
Time Frame: Up to week 84
|
Loss of HBsAg confirmed on 2 consecutive visits at least 12 weeks apart at any time off therapy (HBIg and pegIFN)
|
Up to week 84
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Change in HBsAg from baseline to 48 weeks off peginterferon therapy
Time Frame: Week 84
|
Change in log10 HBsAg from baseline to 48 weeks off peginterferon therapy
|
Week 84
|
Change in HBsAg from baseline to 24 weeks off peginterferon therapy
Time Frame: Week 60
|
Change in log10 HBsAg from baseline to 24 weeks off peginterferon therapy
|
Week 60
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Liu J, Yang HI, Lee MH, Lu SN, Jen CL, Batrla-Utermann R, Wang LY, You SL, Hsiao CK, Chen PJ, Chen CJ; R.E.V.E.A.L.-HBV Study Group. Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma. Gut. 2014 Oct;63(10):1648-57. doi: 10.1136/gutjnl-2013-305785. Epub 2013 Nov 13.
- Rehermann B. Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells. Nat Med. 2013 Jul;19(7):859-68. doi: 10.1038/nm.3251.
- Liang TJ, Block TM, McMahon BJ, Ghany MG, Urban S, Guo JT, Locarnini S, Zoulim F, Chang KM, Lok AS. Present and future therapies of hepatitis B: From discovery to cure. Hepatology. 2015 Dec;62(6):1893-908. doi: 10.1002/hep.28025. Epub 2015 Oct 27.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Hepatitis, Chronic
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antiviral Agents
- Antineoplastic Agents
- Immunologic Factors
- Interferons
- Interferon-alpha
- Antibodies
- Immunoglobulins
- Immunoglobulins, Intravenous
- gamma-Globulins
- Rho(D) Immune Globulin
Other Study ID Numbers
- 180116
- 18-DK-0116
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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