Clinical trial NCT02097004: Study of Therapeutic Vaccination With Intensified Schedule Plus Pegasys Dual Therapy on Chronic Hepatitis B Infection
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis B, Chronic
Keywords: chronic hepatitis B
Pegasys
Euvax B
Baracrude
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2014-03-26
Enrollment: 111
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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)

Eligibility criteria: 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

Primary outcomes:
measure: The rate of HBsAg-seroclearance
timeFrame: The rate of HBsAg-seroclearance at the time point of at weeks 100
Secondary outcomes:
measure: The rate of HBsAg-seroconversion
timeFrame: The rate of HBsAg-seroconversion at weeks 100
measure: The change of HBsAg level from baseline
timeFrame: The change of HBsAg level from baseline at weeks 100
measure: The change of HBsAg-seroclearance
timeFrame: 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
measure: The change of HBsAg-seroconversion
timeFrame: 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
measure: The change of HBsAg level
timeFrame: 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
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University
Study officials:
affiliation: Seoul National University Hospital
name: Yoon Jun Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.