Addition of PegIFN Alfa-2a to CHB Patients Treated With Nucleot(s)Ides

Phase 4

• Conditions: Hepatitis B
• Interventions: Drug: PegIFN alfa-2a

• Registration Number: NCT02644538
• Lead Sponsor: The Second Affiliated Hospital of Chongqing Medical University

Brief Summary

This study evaluates whether PegIFN alfa-2a add on can improve CHB patients HBsAg clearance at the end of 48 weeks treatment. The CHB patients who received nucleot(s)ides anti-virus treatment and reached HBV DNA\<1000 copies/ml and HBsAg\<3000 IU/ml, were randomly assigned into two groups: One group continue the nucleot(s)ides treatment for 72 weeks, the other add on PegIFN alfa-2a on the basis of the original treatment for 48 weeks, and follow up for 24 weeks.

Detailed Description

nucleot(s)ides is a potent inhibitor of hepatitis B viral(HBV) replication, but long-term therapy may be required, and it is difficult for CHB patients to achieve HBsAg clearance by using nucleot(s)ides. Therefore, it is need take long-term therapy if chronic hepatitis B (CHB) choose to use nucleot(s)ides, and in another way, nucleot(s)ides resistance is an important clinical risk. More and more young patients want to stop treating, and discontinuation of nucleot(s)ides is a feasible strategy to reduce resistance. However, it is really easy to relapse if patients did not arrive HBsAg clearance. PegIFN alfa-2a can clear HBV by direct anti-viral and immune regulation mechanisms including enhancing natural killer cell response, increased cluster of differentiation 8(CD8 +) T lymphocytes and other mechanisms to restore and enhance the immune response in patients with CHB; and what's more, patients are safety after discontinuing.

Study Timeline

• Status Verified: 2015-12
• Study Start: 2015-12
• Study First Submitted: 2015-12-28
• Study First Submitted QC: 2015-12-30
• Last Update Submitted: 2015-12-30
• Study First Posted: 2016-01-01
• Last Update Posted: 2016-01-01
• Primary Completion: 2017-12
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 196

Inclusion Criteria

1. Male and female subjects,18-65 years
2. positive for hepatitis B surface antigen (HBsAg) and negative for antibodies to HBsAg (anti-HBs antibodies) for at least 6 months before NAs treated
3. nucleot(s)ides monotherapy (including lamivudine, adefovir, entecavir, tenofovir) and achieved HBV DNA<1000 copies/mL with HBsAg <3000 IU/mL, positive or negative for HBeAg, and negative for anti-HBs antibodies
4. Subjects with no contra-indications to Peginterferon alfa therapy as detailed in the label (Hypersensitivity to the active substance, to alpha interferon, or to any of the excipients; Autoimmune hepatitis; Severe hepatic dysfunction or decompensated cirrhosis of the liver; A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous six months)
5. Subjects who are not co-infected with Hepatitis A Virus, Hepatitis C Virus or HIV
6. Female subjects not pregnant or breast feeding when Peginterferon alfa treatment commenced, and aware of the requirement to use an effective method of contraception during therapy
7. Written informed consent signed.

Exclusion Criteria

1. positive for Hepatitis A Virus Ab, HCV-RNA or positive for Hepatitis C Virus Ab, HDV Ab, HEV Ab or positive for HIV Ab in screening period
2. Hepatocellular carcinoma(HCC) or alpha feto protein(AFP) levels more than 100 ng/ml and Hepatic malignant potential of Imaging examination or AFP levels more than 100 ng/ml for 3 months
3. Compensated or Decompensated liver cirrhosis: with history of cirrhosis before nucleot(s)ides treatment or Child-Pugh score ≥ 5 or Complications of liver cirrhosis such as ascites, hepatic encephalopathy, esophageal gastric varices bleeding
4. Autoimmune disease including Autoimmune hepatitis and Psoriasis and so on
5. Pregnant women and lactating women or patients with pregnancy plans and not willing to use contraception during the study period
6. A history of immunoregulation drug therapy within one year before entry including IFN and so on
7. Have a history of alcohol abuse
8. With severe psychiatric condition or nervous disease such as epilepsy, depression, mania, epilepsy, schizophrenia and so on
9. A neutrophil count of less than 1500 per cubic millimeter or a platelet count of less than 90,000 per cubic millimeter
10. Severe organ dysfunction
11. With other malignant tumors(exclude the cured ones)
12. Uncontrolled diabetes, hypertension or thyroid disease
13. A serum creatinine level that was more than 1.5 times the upper limit of the normal range
14. Hypersensitivity to interferon(IFN) or its active substance, and ineligible to IFN
15. Participate in other clinical studies at the same time
16. Patients unsuitable for the research -

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PegIFN alfa-2a + nucleot(s)ides treated	PegIFN alfa-2a	patients who treated with nucleot(s)ides (including lamivudine, adefovir, entecavir, tenofovir), then will add PegIFN alfa-2a to the original nucleot(s)ides for 48 weeks, then follow up for 24 weeks

Primary Outcome Measures

Name	Time	Method
Number of participants who achieve HBsAg clearance	treat for 48 weeks	To investigate whether Peg-IFN alfa-2a add on treatment can improve the HBsAg clearance in CHB patients at the end of the treatment (48 week).

Secondary Outcome Measures

Name	Time	Method
Number of participants who achieve HBsAg seroconversion	48 weeks	To investigate whether Peg-IFN alfa-2a add on treatment can improve the HBsAg seroconversion in CHB patients at the end of the treatment (48 week).
Number of participants who achieve HBeAg clearance and seroconversion	48 weeks	To investigate whether Peg-IFN alfa-2a add on treatment can improve HBeAg clearance and seroconversion at the end of the treatment (48 week).
HBsAg changes from Baseline	12,24 and 48 weeks	Pegasys 24 weeks Group:12,24 weeks and Pegasys 48 weeks Group:12,24,48 weeks
Number of participants who achieve HBV DNA<1000 copies/ml	12,24 and 48 weeks	To investigate whether Peg-IFN alfa-2a add on treatment can improve HBV DNA\<1000 copies/ml