Clinical trial NCT02644538: Addition of PegIFN Alfa-2a to CHB Patients Treated With Nucleot(s)Ides
Official title: A Randomized, Controlled, Open-label, Multicenter Clinical Trial to Evaluate the Addition of PegIFN Alfa-2a to CHB Patients Treated With Nucleot(s)Ides
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hepatitis B
Keywords: HBsAg clearance
Lead sponsor: The Second Affiliated Hospital of Chongqing Medical University
Sponsor class: OTHER
Collaborators: name: People's Hospital of Anshun City of Guizhou Province
name: The First Affiliated Hospital of Nanchang University
name: First Affiliated Hospital of Xinjiang Medical University
First posted: 2016-01-01
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 -

Primary outcomes:
measure: Number of participants who achieve HBsAg clearance
timeFrame: treat for 48 weeks
Secondary outcomes:
measure: Number of participants who achieve HBsAg seroconversion
timeFrame: 48 weeks
measure: Number of participants who achieve HBeAg clearance and seroconversion
timeFrame: 48 weeks
measure: HBsAg changes from Baseline
timeFrame: 12,24 and 48 weeks
measure: Number of participants who achieve HBV DNA<1000 copies/ml
timeFrame: 12,24 and 48 weeks
Other outcomes:
Locations:
Study officials:
References:
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