Peginterferon Treatment Study for Inactive Chronic Hepatitis B Patients

Hepatitis B, Chronic Clinical Trial

Official title:

Real World Study of Peginterferon Alpha-2b Treatment for Inactive Chronic Hepatitis B Patients: E-Cure Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05182463
• Other study ID #: [2021]02-373-01
• Status: Recruiting
• Phase: Phase 4
• Start date: January 8, 2022
• Est. completion date: November 30, 2029

Study information

• Verified date: April 2022
• Source: Third Affiliated Hospital, Sun Yat-Sen University
• Contact: Zhishuo Mo, Master
• Phone: +86 13632434363
• Email: vbstone[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There are about 400 million chronic hepatitis B virus (HBV) infection patients worldwide, posing a serious threat to global public health security. In China, HBV infection occured mainly in the perinatal period or infants, and about 10% of patients in the immune tolerance stage spontaneously transit to the immune clearance stage every year and become HBeAg-negative chronic HBV infection, resulting in a significant increase in the number of inactive chronic hepatitis B (CHB) patients.

In recent years, different guidelines have not reached consensus on the need to initiate antiviral therapy for inactive CHB patients: In the guidelines of Asian Pacific Association for The Study of Liver(APASL)-2015 and American Association for the Study of Liver Diseases(AASLD)-2018, antiviral therapy is generally not recommended for this group of patients, and regular outpatient follow-up is recommended. Guideline of European Association for the Study of the Liver(EASL)-2017 suggests that people with a family history of cirrhosis and liver cancer at this stage could be treated with antiviral therapy even if they did not meet the indications of antiviral therapy. According to Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2019) of China, antiviral therapy is still recommended for some patients with inactive HBsAg carrier status who are HBV DNA positive and meet the treatment indications. Studies have shown that some patients in immune tolerance stage may enter the immune clearance stage and have hepatitis flare. Patients of inactive CHB have the potential to develop HBeAg-negative CHB, and studies of long-term follow-up in this population have indicated the risk of hepatocellular carcinoma. With the popularization of the concept of functional cure for chronic hepatitis B, more and more people with inactive CHB have a strong desire for treatment. In recent years, several studies have demonstrated that Pegylated-interferon therapy can achieve high functional cure rate in patients with inactive CHB.

The purpose of this study is to establish a national multi-center, prospective real world study to compare the efficacy of different antiviral treatment regimens for patients with inactive CHB and seek for the factors of functional cure.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5000
• Est. completion date: November 30, 2029
• Est. primary completion date: December 13, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Age 18-60, no gender limitation

• HBsAg is positive for more than 6 months

• Hepatitis B e antigen(HBeAg) is negative and anti-HBe is positive

• Serum HBV DNA is less than 2000 IU/mL

• Alanine aminotransferase(ALT) and/or Aspartate aminotransferase(AST) is normal

• No antiviral durg (including nucleos(t)ide analogue and interferon) was used before enrollment

• Good compliance and voluntarily signed informed consent

Exclusion Criteria:

• Allergic to pegylated interferon a-2b

• Any indication of liver cirrhosis

• Coinfection with hepatitis A virus(HAV), hepatitis C virus(HCV), hepatitis D virus(HDV), hepatitis E virus(HEV) or human immunodeficiency virus(HIV)

• Combined with other liver diseases (including drug-related, alcoholic, autoimmune, genetic metabolic liver diseases, etc.)

• There are serious lesions in the important organs, such as heart, lung, kidney, brain and fundus

• Patients with autoimmune diseases, unstable diabetes or thyroid diseases(hyperthyroidism or hypothyroidism)

• Confirmed or suspected liver cancer or other malignant tumors

• Patients after or preparing for organ transplantation

• Peripheral blood white blood cell count < 3.5×109/L and/or platelet count < 80×109/L

• Under immunosuppressant treatment

• Pregnant or planned pregnancy in a short term or lactation patients

• Alcohol abuse (average alcohol intake is more than 40 g/d in males or 20g/d in women) or drug addicts

• Present or past history of mental or psychological diseases

• Other conditions that the investigators deem inappropriate for the study.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Peginterferon Alfa-2B
Different usage of peginterferon Alfa-2B and/or Nucleos(t)ide analogs in arm/group descriptions are depended on the wishes of the patient and the advice of the attending doctor.
• Nucleoside Analogs
Nucleos(t)ide analogs refer to one of the first-line drugs, including ETV, TDF and TAF.

Locations

Country	Name	City	State
China	Department of Infectious Diseases, The Third Affliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Third Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

References & Publications (6)

Cao Z, Liu Y, Ma L, Lu J, Jin Y, Ren S, He Z, Shen C, Chen X. A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha. Hepatology. 2017 Oct;66(4):1058-1066. doi: 10.1002/hep.29213. Epub 2017 Aug 26. — View Citation

Huang Y, Qi M, Liao C, Xun J, Zou J, Huang H, Long LY, Chen J, Fan X, Chen R. Analysis of the Efficacy and Safety of PEGylated Interferon-a2b Treatment in Inactive Hepatitis B Surface Antigen Carriers. Infect Dis Ther. 2021 Dec;10(4):2323-2331. doi: 10.1007/s40121-021-00511-w. Epub 2021 Aug 4. — View Citation

Li MH, Xie Y, Zhang L, Lu Y, Shen G, Wu SL, Chang M, Mu CQ, Hu LP, Hua WH, Song SJ, Zhang SF, Cheng J, Xu DZ. Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a. World J Hepatol. 2016 May 28;8(15):637-43. doi: 10.4254/wjh.v8.i15.637. — View Citation

Liu J, Lee MH, Batrla-Utermann R, Jen CL, Iloeje UH, Lu SN, Wang LY, You SL, Hsiao CK, Yang HI, Chen CJ. A predictive scoring system for the seroclearance of HBsAg in HBeAg-seronegative chronic hepatitis B patients with genotype B or C infection. J Hepatol. 2013 May;58(5):853-60. doi: 10.1016/j.jhep.2012.12.006. Epub 2012 Dec 13. — View Citation

Wu F, Lu R, Liu Y, Wang Y, Tian Y, Li Y, Li M, Wang W, Zhang X, Jia X, Dang S. Efficacy and safety of peginterferon alpha monotherapy in Chinese inactive chronic hepatitis B virus carriers. Liver Int. 2021 Sep;41(9):2032-2045. doi: 10.1111/liv.14897. Epub 2021 May 26. — View Citation

Zeng QL, Yu ZJ, Shang J, Xu GH, Sun CY, Liu N, Li CX, Lv J, Liu YM, Liang HX, Li ZQ, Pan YJ, Hu QY, Li W, Zhang DW, Wang FS. Short-term Peginterferon-Induced High Functional Cure Rate in Inactive Chronic Hepatitis B Virus Carriers With Low Surface Antigen Levels. Open Forum Infect Dis. 2020 Jun 3;7(6):ofaa208. doi: 10.1093/ofid/ofaa208. eCollection 2020 Jun. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HBsAg clearance rate	HBsAg is detected by Roche or Abbott productions, of which the lower limit is 0.05 IU/ml	From date of the beginning of treatment until the date of the end of treatment, assessed up to 96 weeks
Secondary	HBsAg serological conversion rate	HBsAg is detected by Roche or Abbott productions, of which the lower limit is 0.05 IU/ml	From date of the beginning of treatment until the date of the end of treatment, assessed up to 96 weeks
Secondary	The magnitude of HBsAg decline from baseline	HBsAg is detected by quantitative assays from Roche or Abbott	through treatment completion, an anticipated period of 96 weeks
Secondary	The magnitude of HBV-DNA decline from baseline and the undetectable rate	HBV-DNA is detected by assays from Roche or Abbott, of which the lower limit is 15 or 10 IU/ml.	through treatment completion, an anticipated period of 96 weeks
Secondary	HBsAg clearance rate, HBsAg serological conversion rate and maintenance response rate of HBsAg clearance	HBsAg is detected by Roche or Abbott productions, of which the lower limit is 0.05 IU/ml	through follow-up completion, an anticipated period of 144 weeks