Switch or Sequential Combination Therapy of Peginterferon in Hepatitis B Patients With Longterm Entecavir Therapy

Chronic Hepatitis B Clinical Trial

Official title:

Efficacy of Switch or Sequential Combination Therapy of Pegylated Interferon Alfa-2a in Chronic Hepatitis B Patients With Low HBsAg and HBeAg Titers After Long-term Entecavir Therapy: A Multicenter, Prospective Cohort Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02589652
• Other study ID #: 81271833
• Status: Not yet recruiting
• Phase: N/A
• First received: October 25, 2015
• Last updated: October 27, 2015
• Start date: October 2015
• Est. completion date: October 2017

Study information

• Verified date: October 2015
• Source: Huashan Hospital
• Contact: Yiqi Yu, MD
• Phone: +86 21 52888123
• Email: 07301010205[@]fudan.edu.cn
• Is FDA regulated: No
• Health authority: China: Ministry of Science and Technology
• Study type: Observational

Clinical Trial Summary

This is a multicenter, prospective cohort study to evaluate the efficacy and safety of sequential combination or switch therapy of pegylated interferon alfa-2a in chronic hepatitis B patients with low HBsAg and HBeAg titers after long-term entecavir therapy, and compared to those who continued on ETV therapy.

Description:

Chronic hepatitis B (CHB) infection remains a global health treat. The ideal end point of therapy is HBsAg loss or HBsAg seroconversion, indicating a complete remission of CHB. In patients with HBeAg-positive CHB, sustained HBeAg seroconversion is also a desirable end point. Current therapies include pegylated interferon (PegIFN) finite and nucleos(t)ide analogues (NUCs) longterm therapy. However, only 30-40% of patients may achieve HBeAg seroconversion on PegIFN monotherapy, whereas 15-20% of patients on entecavir (ETV). Recently, accumulating evidence had shown that optimization of switching or combining PegIFN in patients on long-term ETV therapy may increase rate of HBeAg seroconversion and even lead to the complete eradication of HBV. However, these two regimens has not been tested adequately in patients with low HBsAg/HBeAg titers on long-term ETV therapy.

This is a multicenter, prospective cohort study to evaluate the efficacy and safety of sequential combination or switch therapy of pegylated interferon alfa-2a in chronic hepatitis B patients with low HBsAg and HBeAg titers after long-term entecavir therapy, and compared to those who continued on ETV therapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 294
• Est. completion date: October 2017
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Male and female patients > 18 and = 60 years of age;

• Positive HBsAg for more than 6 months;

• Patients receiving previous ETV therapy =2 years;

• Patients who have achieved undetectable HBV DNA, HBsAg <1500IU/mL and HBeAg <200S/CO prior to switch or S-C therapy;

• ALT<=10*ULN and TB<2*ULN;

• Patients who have been assigned to treatment with PegIFN (S-C or switch) or continuous ETV after previous ETV therapy

Exclusion Criteria:

• Evidence of decompensated cirrhosis or hepatocellular carcinoma;

• Serological evidence of co-infection with HCV, HDV or HIV;

• Pregnant or breast-feeding women;

• Patients with diseases that might contraindicate to PegIFN therapy including severe psychiatric diseases, immunological diseases, severe retinopathy, thyroid dysfunction, leukocytopenia, thrombopenia, etc

• Patients receiving concomitant therapy with telbivudine;

• A history of drug or alcohol abuse;

• Other conditions that investigates consider not suitable for participate

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

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

Intervention

Drug:
• Pegylated interferon alfa-2a
ETV 0.5mg oral daily plus PegIFN alfa-2a 180ug subcutaneous injection weekly for 8 weeks and followed by PegIFN alfa-2a 180ug subcutaneous injection weekly for 40 weeks
• Pegylated interferon alfa-2a plus Entecavir
ETV 0.5mg oral daily plus PegIFN alfa-2a 180ug subcutaneous injection weekly for 48 weeks
• Entecavir
ETV 0.5mg oral daily for 48 weeks

Locations

Country	Name	City	State
China	Beijing Ditan Hospital	Beijing	Beijing
China	Fuzhou Municipal Infectious Disease Hospital	Fuzhou	Fujian
China	Zhongshan No.2 People's Hospital, Zhongshan, Guangdong	Guangzhou	Guangdong
China	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	The First Affiliated Hospital, Anhui Medical University	Hefei	Anhui
China	The Second Affiliated Hospital, Anhui Medical University	Hefei	Anhui
China	Shandong Provincial Hospital of Shandong University	Jinan	Shandong
China	The Affiliated Hospital of Luzhou Medical College	Luzhou	Sichuan
China	The Second Hospital of Yinzhou of Ningbo	Ningbo	Zhejiang
China	Rui'an People's Hospital	Rui'an	Zhejiang
China	Shenyang Municipal Infectious Disease Hospital	Shenyang	Liaoning
China	The third People's Hospital of Shenzhen	Shenzhen	Guangdong
China	The Third Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Sichuan Provincial People's Hospital	Sichuan	Sichuan
China	Fifth People's Hospital of Suzhou	Suzhou	Jiangsu
China	The First Affiliated Hospital Medical School of Xi'an Jiaotong University	Xi'an	Shanxi
China	The Affiliated Hospital of Xuzhou Medical College	Xuzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Huashan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of HBeAg seroconversion	Loss of HBeAg and detection of anti-HBe antibodies	week 72 (24 weeks after 48 weeks of treatment)	No
Secondary	Rate of HBsAg loss	HBsAg loss with or without detection of anti-HBs antibodies	week 72 (24 weeks after 48 weeks of treatment)	No
Secondary	Rate of HBV DNA <20IU/mL		week 72 (24 weeks after 48 weeks of treatment)	No
Secondary	Rate of HBsAg seroconversion		week 72 (24 weeks after 48 weeks of treatment)	No
Secondary	Percentage of patients reaching a = 1log10 decline of quantitative HBsAg		week 72 (24 weeks after 48 weeks of treatment)	No
Secondary	Decline of quantitative HBsAg from baseline		week 72 (24 weeks after 48 weeks of treatment	No