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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Pegylated interferon alfa-2a
* Drug: Pegylated interferon alfa-2a plus Entecavir
* Drug: Entecavir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Switch group<br>Patients who have been assigned to pegylated interferon alfa-2a. | Drug: Pegylated interferon alfa-2a<br>* 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<br>* Other names: PegIFN alpha-2a;|
| Sequential combination group (S-C group)<br>Patients who have been assigned to pegylated interferon alfa-2a plus entecavir. | Drug: Pegylated interferon alfa-2a plus Entecavir<br>* ETV 0.5mg oral daily plus PegIFN alfa-2a 180ug subcutaneous injection weekly for 48 weeks<br>* Other names: ETV;|
| ETV group<br>Patients who have been assigned to entecavir monotherapy. | Drug: Entecavir<br>* ETV 0.5mg oral daily for 48 weeks<br>* Other names: ETV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of HBeAg seroconversion | Loss of HBeAg and detection of anti-HBe antibodies | week 72 (24 weeks after 48 weeks of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of HBsAg loss | HBsAg loss with or without detection of anti-HBs antibodies | week 72 (24 weeks after 48 weeks of treatment) | 
| Rate of HBV DNA <20IU/mL |  | week 72 (24 weeks after 48 weeks of treatment) | 
| Rate of HBsAg seroconversion |  | week 72 (24 weeks after 48 weeks of treatment) | 
| Percentage of patients reaching a ≥ 1log10 decline of quantitative HBsAg |  | week 72 (24 weeks after 48 weeks of treatment) | 
| Decline of quantitative HBsAg from baseline |  | week 72 (24 weeks after 48 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pegylated interferon, Entecavir