Combination Therapy With Interferon Plus Interleukin 2 and Hepatitis B Vaccine in Chronic Hepatitis B Patients

NCT ID: NCT02360592

Last Updated: 2018-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2017-04-30

Brief Summary

This study is a multi-center, randomized, prospective, open-label Phase IV Clinical trial to evaluate efficacy and safety of interferon alfa-2b therapy combinated with interleukin 2 and hepatitis B therapeutic vaccine versus interferon alfa-2b alone in chronic hepatitis B patients with entecavir achieving HBeAg seroclearance. Patients were randomized to one of 3 groups to receive different antiviral treatment.

Detailed Description

Patients who have been pretreated with entecavir for at least one year, with HBV (Hepatitis B Virus) DNA less than 1000 copies/ml and HBeAg seroclearance were randomized to one of 3 groups, to receive Entecavir 0.5 mg po daily for 72 weeks, or Interferon alfa-2b 600wIU qod iH for 48 weeks plus Entecavir 0.5mg qd po for 8 weeks, or Interferon alfa-2b 600wIU qod iH for 48 weeks plus Entecavir 0.5mg qd po for 8 weeks plus interleukin 2 25 wIU qod iH for 12 weeks plus Hepatitis B Vaccine 60ug qm im for 48 weeks.

Conditions

Hepatitis B, Chronic

Study Design

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

Study Groups

1, conventional control group

Entecavir 0.5 mg po daily for 72 weeks

Group Type: ACTIVE_COMPARATOR

Entecavir

Intervention Type: DRUG

In arm 1, Entecavir is used for 48 weeks and the follow up 24 weeks as conventional control, In arm 2 and 3, Entecavir is used for 8 weeks.

2, combination and sequential group

Interferon alfa-2b 600wIU qod iH for 48 weeks plus Entecavir 0.5mg qd po for 8 weeks

Group Type: EXPERIMENTAL

Entecavir

Intervention Type: DRUG

In arm 1, Entecavir is used for 48 weeks and the follow up 24 weeks as conventional control, In arm 2 and 3, Entecavir is used for 8 weeks.

Interferon alfa-2b

Intervention Type: DRUG

In arm 2 and 3, interferon alfa-2b is used for 48 weeks

3, multitarget group

Interferon alfa-2b 600wIU qod iH for 48 weeks plus Entecavir 0.5mg qd po for 8 weeks plus interleukin 2 25 wIU qod iH for 12 weeks plus Hepatitis B Vaccine 60ug qm im for 48 weeks

Group Type: EXPERIMENTAL

Entecavir

Intervention Type: DRUG

In arm 1, Entecavir is used for 48 weeks and the follow up 24 weeks as conventional control, In arm 2 and 3, Entecavir is used for 8 weeks.

Interferon alfa-2b

Intervention Type: DRUG

In arm 2 and 3, interferon alfa-2b is used for 48 weeks

Interleukin 2

Intervention Type: DRUG

In arm 3, Interleukin 2 is used for 12 weeks

Hepatitis B Vaccine

Intervention Type: DRUG

In arm 3, Hepatitis B Vaccine is used for 48 weeks

Interventions

Entecavir

In arm 1, Entecavir is used for 48 weeks and the follow up 24 weeks as conventional control, In arm 2 and 3, Entecavir is used for 8 weeks.

Intervention Type: DRUG

Interferon alfa-2b

In arm 2 and 3, interferon alfa-2b is used for 48 weeks

Intervention Type: DRUG

Interleukin 2

In arm 3, Interleukin 2 is used for 12 weeks

Intervention Type: DRUG

Hepatitis B Vaccine

In arm 3, Hepatitis B Vaccine is used for 48 weeks

Intervention Type: DRUG

Other Intervention Names

ETV; IFN a-2b; IL-2

Eligibility Criteria

Inclusion Criteria

1. Male and female patients from 18 to 65 years of age;

2. Undergoing treatment with entecavir for at least 1 year ;

3. HBsAg(+), HBeAg(+), HBV DNA≥ 100000 copies/ml，ALT≥2 ULN and ≤10 ULN before receiving entecavir treatment;

4. HBV DNA ≤1000 copies/mL;

5. HBeAg (-);

6. HBsAg (+);

7. Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug;

8. Liver biopsy confirmed without cirrhosis (optional);

9. Agree to participate in the study and sign the patient informed consent.

Exclusion Criteria

1. Patients who had NAs resistance;

2. Other antiviral, anti-neoplastic or immunomodulatory treatment (including supra physiologic doses of steroids and radiation) 6 months prior to the first dose of randomized treatment (except for 7 days of acyclovir for herpetic lesions more than 1 month prior to first administration of randomized treatment). Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation are also excluded;

3. Women with ongoing pregnancy or breast-feeding;

4. Co-infection with active hepatitis A, hepatitis C, hepatitis D(Those hospitals which have the ability to do the test will do) and/or human immunodeficiency virus (HIV);

5. ALT >10 ULN;

6. Evidence of decompensated liver disease (Child-Pugh score > 5 ). Child-Pugh > 5 means, if one of the following 6 conditions are met, the patient has to be excluded: a. Serum albumin < 3.5 g/L; b. Prothrombin time > 3 seconds prolonged; c. Serum bilirubin > 34 μ mol/L; d. History of encephalopathy; e. History of variceal bleeding; f. Ascites;

7. History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures, thalassemia);

8. Signs or symptoms of hepatocellular carcinoma, patients with a value of alpha-fetoprotein > 100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months. Patients with values < 20 ng/mL but > 100 ng/mL may be enrolled, if hepatic neoplasia has been excluded by liver imaging;

9. Neutrophil count < 1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening;

10. Hemoglobin < 11.5 g/dL for females and <12.5 g/dL for men;

11. Serum creatinine level > 1.5 ULN in screening period.

12. Phosphorus < 0.65 mmol/L;

13. ANA > 1:100;

14. History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at herapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease;

15. History of a severe seizure disorder or current anticonvulsant use;

16. History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.);

17. History of chronic pulmonary disease associated with functional limitation;

18. Diseases that IFN and Nucleotides or nucleosides are not suitable.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Kawin Technology Share-Holding Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Fujian Cosunter Pharmaceutical Co. Ltd

INDUSTRY

Sponsor Role: collaborator

Tongji Hospital

OTHER

Sponsor Role: lead

Responsible Party

Qin Ning

Director and Chair of Department of Infectious Diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Qin Ning, Ph.D. M.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Infectious Diseases, Tongji Hospital

Locations

Anhui Provincial Hospital

Hefei, Anhui, China

BeiJing YouAn Hospital, Capital Medical University

Beijing, Beijing Municipality, China

First Hospital, Beijing University

Beijing, Beijing Municipality, China

People'S Hospital Under Beijing University

Beijing, Beijing Municipality, China

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

Department of infectious disease, Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Tongji Hospital

Wuhan, Hubei, China

Departmen of infectious disease, Xiangya Hospital, Central-south Universit

Changsha, Hunan, China

ShengJing Hospital of China Medical University

Shenyang, Liaoning, China

Shanghai Ruijin Hospital, Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

The First Affiliated Hospital of College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

The first affiliated hospital of Wenzhou medical universtiy

Wenzhou, Zhejiang, China

Countries

China

Other Identifiers

Endeavor study, a pilot study

Identifier Type: -

Identifier Source: org_study_id