Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Hepatitis B Immune Globulin (HBIg) to Restore Immune Control in People With Chronic Hepatitis 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03575208
Recruitment Status : Recruiting
First Posted : July 2, 2018
Last Update Posted : December 24, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) )

Brief 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.


Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Biological: hepatitis B immune globulin Drug: Pegylated interferon alfa Phase 2

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 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. We will investigate whether this strategy will result in restoration of adaptive and 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 endpoint of the trial will be clearance of HBsAg and restoration of the HBV-specific T-cell response.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Use of Hepatitis B Immune Globulin (HBIg) to Restore Immune Control in Patients With Chronic Hepatitis B
Actual Study Start Date : February 13, 2019
Estimated Primary Completion Date : August 31, 2021
Estimated Study Completion Date : May 30, 2022


Arm Intervention/treatment
Experimental: Arm 1
HBIg x 12 weeks followed by peginterferon alfa-2a 180ug x 24 weeks
Biological: hepatitis B immune globulin
HBIg 20,000 U/L iv. Dosing interval will depend on anti-HBs levels.

Drug: Pegylated interferon alfa
peginterferon alfa-2a 180ug sq q weekly for 24 weeks

Experimental: Arm 2
peginterferon alfa-2a 180ug x 24 weeks
Drug: Pegylated interferon alfa
peginterferon alfa-2a 180ug sq q weekly for 24 weeks




Primary Outcome Measures :
  1. Restoration of T cell response [ Time Frame: 4 weeks after HBlg ]
    Restoration of T cell response

  2. Clearance of Hepatitis B surface antigen [ Time Frame: 48 wks after pegIFN ]
    Loss of HBsAg


Secondary Outcome Measures :
  1. Decline in HBsAg levels [ Time Frame: at the end of treatment with HBIg, at end-of-treatment with peginterferon and 24 and 48 weeks off peginterferon therapy ]
  2. Correlation of HBsAg levels with T-cell response [ Time Frame: 4-12 wks after HBIg ]
  3. Sustained suppression of HBV DNA [ Time Frame: 48 wks after pegIFN ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Age >18, male or female
    2. Known serum HBsAg positive with a level <1,500 IU/mL at the time of screening
    3. Hepatitis B e antigen negative; anti-HBe positive at the time of screening
    4. HBV DNA levels <2000 IU/mL on two occasions at least 24 weeks apart with the second being at time of screening
    5. ALT level less than or equal to 1.5 ULN based on at least two determinations taken at least 24 weeks apart during the 24 weeks before study entry with the second being at time of screening
    6. Written informed consent

EXCLUSION CRITERIA:

  1. Any treatment for HBV within the last 48 weeks
  2. Co-infection with HDV as defined by the presence of anti-HDV in serum.
  3. Co-infection with HCV as defined by the presence of anti-HCV with HCV RNA in serum.
  4. Co-infection with HIV as defined by the presence of anti-HIV in serum.
  5. Presence of anti-HBs in serum
  6. Cirrhosis either diagnosed by a prior liver biopsy at any time or if not available by a transient elastography score >13 kPa.
  7. 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.
  8. Presence of other causes of liver disease, (i.e. hemochromatosis, Wilson disease, alcoholic liver disease, alpha-1-anti- trypsin deficiency).
  9. 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.
  10. Severe IgA deficiency
  11. Severe allergic reaction to any human immunoglobulin product
  12. 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.
  13. Pregnancy or inability to practice 2 forms of contraception in women capable of bearing children
  14. Lactating women.
  15. 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.
  16. eGFR < 50 ml/min, serum creatinine > 1.3 mg/dl
  17. History of hypersensitivity to pegylated interferon-alpha
  18. Platelet count <90 mm(3)/dL
  19. Hgb <12 g/dL for males and <11 g/dL for females
  20. 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.
  21. 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).
  22. 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.
  23. Presence of conditions that, in the opinion of the investigators, would not allow the patient to be followed in the current study.

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 ClinicalTrials.gov identifier (NCT number): NCT03575208


Contacts
Layout table for location contacts
Contact: Amy (Wen-Chun) Huang (301) 451-6983 wen-chun.huang@nih.gov

Locations
Layout table for location information
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Layout table for investigator information
Principal Investigator: Marc G Ghany, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional Information:
Layout table for additonal information
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT03575208    
Other Study ID Numbers: 180116
18-DK-0116
First Posted: July 2, 2018    Key Record Dates
Last Update Posted: December 24, 2019
Last Verified: December 20, 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ):
Hepatitis B
Immune Response
HBsAg Loss
Hepatitis B Virus
Interferon
Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Interferons
Interferon-alpha
Peginterferon alfa-2a
Immunoglobulins
Antibodies
gamma-Globulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunoglobulin G
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs