Clinical trial NCT02893124: The Optimizing Treatment of Peginterferon (PEG IFN) Alpha in Chronic Hepatitis B Virus Patients With Low Level HBsAg
Official title: The Optimizing Treatment of Peginterferon Alpha in HBeAg-negative Chronic Hepatitis B Virus Patients With Low Level HBsAg
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis B
Keywords: chronic hepatitis B
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Peking University
name: Huazhong University of Science and Technology
name: Nanchang University
name: Huizhou Municipal Central Hospital
name: First People's Hospital, Shunde China
name: Shenzhen Third People's Hospital
name: First People's Hospital of Foshan
name: Tang-Du Hospital
name: First Affiliated Hospital of Kunming Medical University
name: Yuebei People's Hospital
First posted: 2016-09-08
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: HBeAg-negative chronic hepatitis B (CHB) patients with low Level HBsAg and with a history of drug resistance or suboptimal/partial virological response were enrolled. After giving informed consent, patients were treated with nucleoside analog(s) (NAs) once a day and weekly subcutaneous injections of alfa-2a 180 micrograms/week or peginterferon alfa-2b 80 micrograms/week for 12 weeks. 12 weeks later, NAs was stopped, patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or peginterferon alfa-2b 80 micrograms/week. Treatment endpoint was HBsAg loss(\<0.05 IU/mL).

Detailed description: It is estimated that more than 400 million people are infected with hepatitis B virus (HBV) globally. HBeAg-negative CHB patients with low Level HBsAg and with a history of drug resistance or suboptimal/partial virological response were enrolled in the out-patient department of 3rd Affiliated Hospital of Sun Yat-sen University. All of them were HBsAg positive and anti-HBs negative for more than 6 months with HBV DNA\<100 IU/mL and HBsAg levels \<1000 IU/mL. All patients did not have other liver diseases and contraindications for interferon therapy.

After giving informed consent, patients were treated with NAs once a day and weekly subcutaneous injections of alfa-2a 180 micrograms/week or peginterferon alfa-2b 80 micrograms/week for 12 weeks. 12 weeks later, NAs was stopped, patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or peginterferon alfa-2b 80 micrograms/week. The use of other immune suppressive or regulatory drugs and other antiviral drugs was prohibited during the course of the study.

In this study, treatment endpoint was HBsAg loss(\<0.05 IU/mL).Anti-HBs positive(\>10 milli-International unit)(mIU/mL) defined as seroconversion. Depending on the decline of HBsAg level, treatment was either continued for a prolonged period (no more than 96 weeks) until the endpoint was achieved, or terminated in case of nonresponse.

Eligibility criteria: Inclusion Criteria:

1. CHB patients who had received single NAs for more than 12 months and had a history of NAs drug resistance or suboptimal/partial virological response.
2. Hepatitis B e antigen (HBeAg)-negative.
3. Hepatitis B surface antigen (HBsAg) positive and \<1000 IU/mL.
4. Hepatitis B virus DNA \<100 IU/mL.

Exclusion Criteria:

1. Patients with liver cirrhosis, Hepatocellular Carcinoma or alpha feto protein (AFP) \>2 upper limit of normal(ULN) or other malignancies.
2. Patients with other factors causing liver diseases.
3. Pregnant and lactating women.
4. Patients with concomitant HIV infection or congenital immune deficiency diseases.
5. Patients with diabetes, autoimmune diseases.
6. Patients with important organ dysfunctions.
7. Patients with serious complications (e.g., infection, hepatic encephalopathy, hepatorenal syndrome, gastrointestinal bleeding.)
8. Patients who receive antineoplastic or immunomodulatory therapy in the past 12 months.
9. Patients with a previous use of IFN anti hepatitis B virus treatment.
10. Patients who can't come back to clinic for follow-up on schedule.

Primary outcomes:
measure: HBsAg Clearance
timeFrame: 96 weeks
Secondary outcomes:
measure: HBsAg Seroconversion
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Infectious Diseases, The Third Affliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
References: