Study of Therapeutic Vaccination With Intensified Schedule Plus Pegasys Dual Therapy on Chronic Hepatitis B Infection

NCT ID: NCT02097004

Last Updated: 2018-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 111 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2018-03-13

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)

Conditions

Hepatitis B, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Peginterferon alfa-2a

Intervention Type: BIOLOGICAL

once weekly 180 μg subcutaneous injection for 48 weeks

HBV vaccination

Intervention Type: BIOLOGICAL

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

Entecavir

Intervention Type: DRUG

Continue Entecavir(0.5mg) for 100 weeks

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)

Group Type: EXPERIMENTAL

Peginterferon alfa-2a

Intervention Type: BIOLOGICAL

once weekly 180 μg subcutaneous injection for 48 weeks

HBV vaccination

Intervention Type: BIOLOGICAL

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

Entecavir

Intervention Type: DRUG

Continue Entecavir(0.5mg) for 100 weeks

Control Group

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

Group Type: ACTIVE_COMPARATOR

Peginterferon alfa-2a

Intervention Type: BIOLOGICAL

once weekly 180 μg subcutaneous injection for 48 weeks

Entecavir

Intervention Type: DRUG

Continue Entecavir(0.5mg) for 100 weeks

Interventions

Peginterferon alfa-2a

once weekly 180 μg subcutaneous injection for 48 weeks

Intervention Type: BIOLOGICAL

HBV vaccination

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

Intervention Type: BIOLOGICAL

Entecavir

Continue Entecavir(0.5mg) for 100 weeks

Intervention Type: DRUG

Other Intervention Names

Pegasys; Euvax B Inj; Baracrude

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seoul National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yoon Jun Kim

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yoon Jun Kim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

Locations

Seoul National University

Seoul, , South Korea

Countries

South Korea

References

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.

Reference Type: DERIVED

PMID: 32556157 (View on PubMed)

Other Identifiers

E+VIP

Identifier Type: -

Identifier Source: org_study_id