Study of Therapeutic Vaccination With Intensified Schedule Plus Pegasys Dual Therapy on Chronic Hepatitis B Infection (E+VIP)

May 3, 2018 updated by: Yoon Jun Kim, Seoul National University Hospital

Phase4, to Compare Efficacy and Safety of Therapeutic Vaccination With Intensified Schedule Plus Pegylated Interferon Dual Therapy on Seroclearance of HBS Antigen in Patients With Complete Virological Response Induced by Entecavir

A randomized, Open label, Single center, Prospective study to compare efficacy and safety of Therapeutic Vaccination with Intensified schedule plus Pegylated Interferon dual Therapy on Seroclearance of Hepatitis B virus Surface Antigen in Patients with Complete Virological Response Induced by Entecavir

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A randomized, Open label, Single center, Prospective study to compare efficacy and safety of Therapeutic Vaccination with Intensified schedule plus Pegylated Interferon dual Therapy on Seroclearance of Hepatitis B virus Surface Antigen in Patients with Complete Virological Response Induced by Entecavir (E + VIP)

Study Type

Interventional

Enrollment (Actual)

111

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age between 20 and 75 year-old
  2. HBsAg-positive for > 6 months apart (medical history can be alternative)
  3. Currently being treated with entecavir 0.5 mg/day for more than 18 months
  4. Undetectable HBV DNA in serum (<20IU/mL) and HBeAg-negative or positive for > 1year
  5. HBsAg titer < 3,000 IU/mL
  6. ALT<300 IU/L
  7. Signed written informed consent after being instructed about the objective and procedure of the clinical study

Exclusion Criteria:

  1. Patients with decompensated liver cirrhosis, any one of the following ① Serum bilirubin > 3 mg/dL

    ② Prothrombin time > 6 seconds prolonged or INR >2.3

    ③ Serum albumin < 2.8 g/dL

    ④ History of ascites, variceal hemorrhage, or hepatic encephalopathy

    ⑤ Child-Pugh score ≥7 (Child-Pugh class B or C)

  2. Patients who have evidence of renal insufficiency defined as serum creatinine>1.5 mg/dL
  3. Patients with psychological problem including depression
  4. Patients who have previous/current significant co-morbidities including congestive heart failure, chronic kidney disease, hematologic disease and malignancy including hepatocellular carcinoma(patients with malignancy cured 5 years before screening can be enrolled)
  5. Patients with seropositivity for anti-HCV, anti-HDV or anti-HIV
  6. Patients who have excessive alcohol consumption (> 30 g/day)
  7. Patients who have evidence of autoimmune hepatitis, hemochromatosis or Wilson's disease
  8. Pregnant or breast feeding females or plan for pregnancy or no contraception
  9. Patients with disease may deteriorate with interferon therapy(eg, autoimmune thyroiditis)
  10. Patients who have an psoriasis
  11. Patients who have history of antiviral-resistant HBV after previous treatment with oral antiviral agents
  12. Previous diagnosis with immunodeficiency or concomitant treatment of immune suppressive agent or previous organ transplantation Recipients
  13. Patients who have a history of hypersensitivity to study drug
  14. Uncontrollable seizure, convulsion and/or central nervous system disorders
  15. Patients with severe bone marrow disorder or with history of hypersensitivity to biologic agent such as vaccine.
  16. Neutrophil count < 1,500/mm3 or platelet count < 75,000/mm3 or hemoglobin < 10 g/dl
  17. Patients with Pulmonary disease (in case of history of pulmonary disease with complete recovery, enrollment is on investigator's discretion)
  18. Patients who have a fever ≥ 38 °C at the baseline
  19. Patients who have a risk of febrile response or systemic reaction
  20. Patients who the investigator deems inappropriate to participate in this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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: Concomitant:Pegasys, Euvax B, Baracrude
  • Peginterferon alfa-2a: once weekly 180 μg subcutaneous injection for 48 weeks
  • HBV vaccination (Euvax B Inj): 1.0 mL (20 μg) intramuscular injection at 4, 8, 12 and 28 weeks
  • Continue Entecavir(0.5mg) for 100 weeks(once daily)
Biological: Peginterferon alfa-2a
once weekly 180 μg subcutaneous injection for 48 weeks
Other Names:
  • Pegasys
Biological: HBV vaccination
1.0 mL (20 μg) intramuscular injection at 4, 8, 12 and 28 weeks
Other Names:
  • Euvax B Inj
Drug: Entecavir
Continue Entecavir(0.5mg) for 100 weeks
Other Names:
  • Baracrude
Experimental: Sequential:Pegasys, Euvax B, Baracrude
  • Peginterferon alfa-2a: once weekly 180 μg or weight base dose subcutaneous injection for 48 weeks
  • HBV vaccination (Euvax B Inj): 1.0 mL (20 μg) intramuscular injection at 52, 56, 60 and 76 weeks
  • Continue Entecavir(0.5mg) for 100 weeks(once daily)
Biological: Peginterferon alfa-2a
once weekly 180 μg subcutaneous injection for 48 weeks
Other Names:
  • Pegasys
Biological: HBV vaccination
1.0 mL (20 μg) intramuscular injection at 4, 8, 12 and 28 weeks
Other Names:
  • Euvax B Inj
Drug: Entecavir
Continue Entecavir(0.5mg) for 100 weeks
Other Names:
  • Baracrude
Active Comparator: Control Group
  • Continue Entecavir(0.5mg) for 100 weeks(once daily)
  • After EOS(100W), injection(once weekly) a Peginterferon alfa-2a for 48 weeks
Biological: Peginterferon alfa-2a
once weekly 180 μg subcutaneous injection for 48 weeks
Other Names:
  • Pegasys
Drug: Entecavir
Continue Entecavir(0.5mg) for 100 weeks
Other Names:
  • Baracrude

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The rate of HBsAg-seroclearance
Time Frame: The rate of HBsAg-seroclearance at the time point of at weeks 100
The rate of HBsAg-seroclearance at the time point of at weeks 100 in the sequential treatment group (24 weeks after termination of treatment) versus control group(ETV monotherapy) at weeks 100.
The rate of HBsAg-seroclearance at the time point of at weeks 100

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The rate of HBsAg-seroconversion
Time Frame: The rate of HBsAg-seroconversion at weeks 100
The rate of HBsAg-seroconversion at weeks 100 in the sequential treatment group versus control group(ETV monotherapy) at weeks 100.
The rate of HBsAg-seroconversion at weeks 100
The change of HBsAg level from baseline
Time Frame: The change of HBsAg level from baseline at weeks 100
The change of HBsAg level from baseline at weeks 100 in the sequential treatment group versus control group(ETV monotherapy) at weeks 100.
The change of HBsAg level from baseline at weeks 100
The change of HBsAg-seroclearance
Time Frame: The change of HBsAg-seroclearance at weeks 4, weeks 12, weeks 24, weeks 36, weeks 48, weeks 60, weeks 72, weeks 96, weeks 100, weeks 148
The change of HBsAg-seroclearance in the concomitant treatment group versus control group(ETV monotherapy) for exploratory assessment.
The change of HBsAg-seroclearance at weeks 4, weeks 12, weeks 24, weeks 36, weeks 48, weeks 60, weeks 72, weeks 96, weeks 100, weeks 148
The change of HBsAg-seroconversion
Time Frame: The change of HBsAg-seroconversion at weeks 4, weeks 12, weeks 24, weeks 36, weeks 48, weeks 60, weeks 72, weeks 96, weeks 100, weeks 148
The change of HBsAg-seroconversion in the concomitant treatment group versus control group(ETV monotherapy) for exploratory assessment.
The change of HBsAg-seroconversion at weeks 4, weeks 12, weeks 24, weeks 36, weeks 48, weeks 60, weeks 72, weeks 96, weeks 100, weeks 148
The change of HBsAg level
Time Frame: The change of HBsAg level at weeks 4, weeks 12, weeks 24, weeks 36, weeks 48, weeks 60, weeks 72, weeks 96, weeks 100, weeks 148
The change of HBsAg level in the concomitant treatment group versus control group(ETV monotherapy) for exploratory assessment.
The change of HBsAg level at weeks 4, weeks 12, weeks 24, weeks 36, weeks 48, weeks 60, weeks 72, weeks 96, weeks 100, weeks 148

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2014

Primary Completion (Actual)

January 1, 2018

Study Completion (Actual)

March 13, 2018

Study Registration Dates

First Submitted

March 23, 2014

First Submitted That Met QC Criteria

March 25, 2014

First Posted (Estimate)

March 26, 2014

Study Record Updates

Last Update Posted (Actual)

May 9, 2018

Last Update Submitted That Met QC Criteria

May 3, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • E+VIP

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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