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

Registration Number
NCT02589652
Lead Sponsor
Huashan Hospital
Brief 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.

Detailed 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 & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
294
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

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Switch groupPegylated interferon alfa-2aPatients who have been assigned to pegylated interferon alfa-2a.
ETV groupEntecavirPatients who have been assigned to entecavir monotherapy.
Sequential combination group (S-C group)Pegylated interferon alfa-2a plus EntecavirPatients who have been assigned to pegylated interferon alfa-2a plus entecavir.
Primary Outcome Measures
NameTimeMethod
Rate of HBeAg seroconversionweek 72 (24 weeks after 48 weeks of treatment)

Loss of HBeAg and detection of anti-HBe antibodies

Secondary Outcome Measures
NameTimeMethod
Rate of HBV DNA <20IU/mLweek 72 (24 weeks after 48 weeks of treatment)
Rate of HBsAg lossweek 72 (24 weeks after 48 weeks of treatment)

HBsAg loss with or without detection of anti-HBs antibodies

Rate of HBsAg seroconversionweek 72 (24 weeks after 48 weeks of treatment)
Percentage of patients reaching a ≥ 1log10 decline of quantitative HBsAgweek 72 (24 weeks after 48 weeks of treatment)
Decline of quantitative HBsAg from baselineweek 72 (24 weeks after 48 weeks of treatment

Trial Locations

Locations (17)

The First Affiliated Hospital, Anhui Medical University

🇨🇳

Hefei, Anhui, China

Fuzhou Municipal Infectious Disease Hospital

🇨🇳

Fuzhou, Fujian, China

The Third Hospital of Hebei Medical University

🇨🇳

Shijiazhuang, Hebei, China

Zhongshan No.2 People's Hospital, Zhongshan, Guangdong

🇨🇳

Guangzhou, Guangdong, China

The Second Affiliated Hospital, Anhui Medical University

🇨🇳

Hefei, Anhui, China

Shandong Provincial Hospital of Shandong University

🇨🇳

Jinan, Shandong, China

Sichuan Provincial People's Hospital

🇨🇳

Sichuan, Sichuan, China

The First Affiliated Hospital, College of Medicine, Zhejiang University

🇨🇳

Hangzhou, Zhejiang, China

Rui'an People's Hospital

🇨🇳

Rui'an, Zhejiang, China

Beijing Ditan Hospital

🇨🇳

Beijing, Beijing, China

Fifth People's Hospital of Suzhou

🇨🇳

Suzhou, Jiangsu, China

The third People's Hospital of Shenzhen

🇨🇳

Shenzhen, Guangdong, China

The Affiliated Hospital of Xuzhou Medical College

🇨🇳

Xuzhou, Jiangsu, China

Shenyang Municipal Infectious Disease Hospital

🇨🇳

Shenyang, Liaoning, China

The First Affiliated Hospital Medical School of Xi'an Jiaotong University

🇨🇳

Xi'an, Shanxi, China

The Affiliated Hospital of Luzhou Medical College

🇨🇳

Luzhou, Sichuan, China

The Second Hospital of Yinzhou of Ningbo

🇨🇳

Ningbo, Zhejiang, China

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