Clinical trial NCT03801538: The Optimizing Treatment of Peginterferon Alpha in Chronic Hepatitis B Patients With Low Level HBsAg
Official title: The Optimizing Treatment of Peginterferon Alpha in Chronic Hepatitis B Patients With Low Level HBsAg(I-Cure-3X)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis B
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Wuhan Union Hospital, China
First posted: 2019-01-11
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 were enrolled. After giving informed consent, patients were treated with nucleoside analog(s) (NAs) once a day and weekly subcutaneous injections of peginterferon alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week for 12 weeks. At week 12, the decrease of HBsAg was evaluated.

①If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped, patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(\<0.05 IU/ mL). 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 week 96. After treatment, all patients were followed up for 48 weeks.

②If the decrease of HBsAg is less than 50% compared to baseline level. The combination therapy of NAs and peginterferon alfa was extended to week 24. Then, the decrease of HBsAg was evaluated again.

If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped, patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(\<0.05 IU/mL). 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 week 96. After treatment, all patients were followed up for 48 weeks.

If the decrease of HBsAg is less than 50% compared to baseline level. Peginterferon alfa was stopped, patients were treated with NAs once a day and then followed up for 48 weeks.

Patients who maintained the original NAs treatment served as a control group.

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 were enrolled in the out-patient department of Third Affiliated Hospital of Sun Yat-sen University and Wuhan Union Hospital. 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 nucleoside analog(s) (NAs) once a day and weekly subcutaneous injections of peginterferon alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week for 12 weeks. At week 12, the decrease of HBsAg was evaluated.

①If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped, patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(\<0.05 IU/ mL). 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 week 96. After treatment, all patients were followed up for 48 weeks.

②If the decrease of HBsAg is less than 50% compared to baseline level. The combination therapy of NAs and peginterferon alfa was extended to week 24. Then, the decrease of HBsAg was evaluated again.

If the decrease of HBsAg is more than 50% compared to baseline level. NAs was stopped, patients were treated with weekly subcutaneous injections of alfa-2a 180 micrograms/week or peginterferon alfa-2b 180 micrograms/week. Treatment endpoint was HBsAg loss(\<0.05 IU/mL). 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 week 96. After treatment, all patients were followed up for 48 weeks.

If the decrease of HBsAg is less than 50% compared to baseline level. Peginterferon alfa was stopped, patients were treated with NAs once a day and then followed up for 48 weeks.

The use of other immune suppressive or regulatory drugs and other antiviral drugs was prohibited during the course of the study. In this study, HBsAg loss(\<0.05 IU/mL) was defined as treatment endpoint. Anti-HBs positive(\>10 milli-International unit)(mIU/mL) was defined as seroconversion.

Patients who maintained the original NAs treatment served as a control group.

Eligibility criteria: Inclusion Criteria:

1. CHB patients who had received NAs for more than 12 months.
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 who can't come back to clinic for follow-up on schedule.

Primary outcomes:
measure: HBsAg Clearance
timeFrame: 96 weeks
measure: HBsAg Seroconversion
timeFrame: 96 weeks
Secondary outcomes:
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:
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Zhiliang Gao
role: PRINCIPAL_INVESTIGATOR
References: