NCT02097004

Brief Summary

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
111

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Apr 2014

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 23, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 26, 2014

Completed
6 days until next milestone

Study Start

First participant enrolled

April 1, 2014

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2018

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 13, 2018

Completed
Last Updated

May 9, 2018

Status Verified

May 1, 2018

Enrollment Period

3.8 years

First QC Date

March 23, 2014

Last Update Submit

May 3, 2018

Conditions

Hepatitis B, Chronic

Keywords

chronic hepatitis BPegasysEuvax BBaracrude

Outcome Measures

Primary Outcomes (1)

  • The rate of HBsAg-seroclearance

    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 Outcomes (5)

  • The rate of HBsAg-seroconversion

    The rate of HBsAg-seroconversion at weeks 100

  • The change of HBsAg level from baseline

    The change of HBsAg level from baseline at weeks 100

  • The change of HBsAg-seroclearance

    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

    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

    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

Study Arms (3)

Concomitant:Pegasys, Euvax B, Baracrude

EXPERIMENTAL

* 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-2aBiological: HBV vaccinationDrug: Entecavir

Sequential:Pegasys, Euvax B, Baracrude

EXPERIMENTAL

* 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-2aBiological: HBV vaccinationDrug: Entecavir

Control Group

ACTIVE COMPARATOR

* 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-2aDrug: Entecavir

Interventions

Peginterferon alfa-2aBIOLOGICAL

once weekly 180 μg subcutaneous injection for 48 weeks

Also known as: Pegasys
Concomitant:Pegasys, Euvax B, BaracrudeControl GroupSequential:Pegasys, Euvax B, Baracrude
HBV vaccinationBIOLOGICAL

1.0 mL (20 μg) intramuscular injection at 4, 8, 12 and 28 weeks

Also known as: Euvax B Inj
Concomitant:Pegasys, Euvax B, BaracrudeSequential:Pegasys, Euvax B, Baracrude
EntecavirDRUG

Continue Entecavir(0.5mg) for 100 weeks

Also known as: Baracrude
Concomitant:Pegasys, Euvax B, BaracrudeControl GroupSequential:Pegasys, Euvax B, Baracrude

Eligibility Criteria

Age20 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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)
  • Patients who have evidence of renal insufficiency defined as serum creatinine\>1.5 mg/dL
  • Patients with psychological problem including depression
  • 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)
  • Patients with seropositivity for anti-HCV, anti-HDV or anti-HIV
  • Patients who have excessive alcohol consumption (\> 30 g/day)
  • Patients who have evidence of autoimmune hepatitis, hemochromatosis or Wilson's disease
  • Pregnant or breast feeding females or plan for pregnancy or no contraception
  • Patients with disease may deteriorate with interferon therapy(eg, autoimmune thyroiditis)
  • Patients who have an psoriasis
  • Patients who have history of antiviral-resistant HBV after previous treatment with oral antiviral agents
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Seoul National University

Seoul, ASI|KR|KS013, South Korea

Location

Related Publications (1)

  • Lee JH, Lee YB, Cho EJ, Yu SJ, Yoon JH, Kim YJ. Entecavir Plus Pegylated Interferon and Sequential Hepatitis B Virus Vaccination Increases Hepatitis B Surface Antigen Seroclearance: A Randomized Controlled Proof-of-Concept Study. Clin Infect Dis. 2021 Nov 2;73(9):e3308-e3316. doi: 10.1093/cid/ciaa807.

    PMID: 32556157DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

peginterferon alfa-2aentecavir

Condition Hierarchy (Ancestors)

Hepatitis BBlood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Yoon Jun Kim, MD, PhD

    Seoul National University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

March 23, 2014

First Posted

March 26, 2014

Study Start

April 1, 2014

Primary Completion

January 1, 2018

Study Completion

March 13, 2018

Last Updated

May 9, 2018

Record last verified: 2018-05

Locations

KR(1)