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Chronic Hepatitis BPhase 2NCT03575208

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

A Phase 2 study testing hepatitis B immune globulin (HBIg) and Pegylated interferon alfa (pegIFN) in people with Chronic Hepatitis B, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Hepatitis B
What is being tested?
hepatitis B immune globulin (HBIg) and Pegylated interferon alfa (pegIFN)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
13 Feb 2019to 29 Mar 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 25Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: 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.

Read more

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.

Read the 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).

Being tested
hepatitis B immune globulin (HBIg), Pegylated interferon alfa (pegIFN)
Keywords
HBsAg Loss, Peginterferon, Inactive Carrier
Medical subject headings
Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • hepatitis B immune globulin (HBIg)Biological

    HBIg 20,000 U/L iv. Dosing interval will depend on anti-HBs levels.

  • Pegylated interferon alfa (pegIFN)Drug

    peginterferon alfa-2a 180 mcg weekly for 24 weeks

Study groups in NCT03575208
Study groupRoleWhat they receive
HBIG followed by Peginterferon alfa-2aExperimentalHBIg x 12 weeks followed by peginterferon alfa-2a 180mcg x 24 weeks
Receives: Biological: hepatitis B immune globulin (HBIg); Drug: Pegylated interferon alfa (pegIFN)
Peginterferon alfa-2aActive comparatorPeginterferon alfa-2a 180mcg x 24 weeks
Receives: Drug: Pegylated interferon alfa (pegIFN)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. NK cell response to the first peginterferon injection both groups

    Change in TRAIL-expressing NK cell within the first 6 hours after the first peginterferon injection

    Measured: 6 hours after the first peginterferon injection

  2. Improvement of HBsAg-specific T cell responses HBIG only group

    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

    Measured: Baseline to week 12

  3. Improvement of HBsAg-specific T cell responses both groups

    Change in the frequency of IFN-g producing T cells from baseline to week 36

    Measured: Baseline to week 36

Secondary outcomes (3)

  1. HBsAg loss

    Loss of HBsAg confirmed on 2 consecutive visits at least 12 weeks apart at any time off therapy (HBIg and pegIFN)

    Measured: Up to week 84

  2. Change in HBsAg from baseline to 48 weeks off peginterferon therapy

    Change in log10 HBsAg from baseline to 48 weeks off peginterferon therapy

    Measured: Week 84

  3. Change in HBsAg from baseline to 24 weeks off peginterferon therapy

    Change in log10 HBsAg from baseline to 24 weeks off peginterferon therapy

    Measured: Week 60

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2018
  2. Study start13 Feb 2019
  3. Primary completion29 Mar 2022
  4. Study completion29 Mar 2022

Why it stopped: Slow/Insufficient accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03575208
Sponsor's protocol ID
180116
Other IDs
18-DK-0116
Status last verified
Apr 2022
First submitted
29 Jun 2018
Last updated
6 Apr 2022
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

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.

    PubMed 24225939

  • 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.

    PubMed 23836236

  • 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.

    PubMed 26239691

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing hepatitis B immune globulin (HBIg) and Pegylated interferon alfa (pegIFN) in people with Chronic Hepatitis B, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 6 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

NK cell response to the first peginterferon injection both groups (time frame: 6 hours after the first peginterferon injection). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03575208, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2022.

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