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

Seoul National University

Status and phase: Completed; Phase 4

Conditions: Hepatitis B, Chronic

Treatments: Drug: Entecavir; Biological: Peginterferon alfa-2a; Biological: HBV vaccination

Study type: Interventional

Funder types: Other

Identifiers

NCT02097004

E+VIP

Details and patient eligibility

About

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

Full 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)

Enrollment: 111 patients

Sex: All

Ages: 20 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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111 participants in 3 patient groups

Concomitant:Pegasys, Euvax B, Baracrude

Experimental group

Description:

* 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)

Treatment:

Biological: HBV vaccination

Biological: Peginterferon alfa-2a

Drug: Entecavir

Sequential:Pegasys, Euvax B, Baracrude

Experimental group

Description:

* 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)

Treatment:

Biological: HBV vaccination

Biological: Peginterferon alfa-2a

Drug: Entecavir

Control Group

Active Comparator group

Description:

* Continue Entecavir(0.5mg) for 100 weeks(once daily) * After EOS(100W), injection(once weekly) a Peginterferon alfa-2a for 48 weeks

Treatment:

Biological: Peginterferon alfa-2a

Drug: Entecavir