The aim of current study is to investigate whether the HBsAg clearance rate can be improved if applying RGT((Response-Guided Therapy) strategy in HBeAg positive CHB(chronic hepatitis B) patients treated by nucleoside analogue(NUC) achieved HBVDNA\<1000copies/ml,and HBsAg\<5000IU/ml; \&HBeAg\<100PEIU/ml (or470s/co), combined with PEG-IFN a-2a for 24 weeks.
The current study is a prospective, randomized, open, multi-center investigation. The aim of current study is to investigate whether the HBsAg clearance rate can be improved if applying RGT strategy in HBeAg positive CHB patients treated by NUC achieved HBVDNA\<1000copies/ml,and HBsAg\<5000IU/ml; \&HBeAg\<100PEIU/ml (or470s/co), combined with PEG-IFN a-2a for 24 weeks. Then the subjects will be divided into three groups according to qHBsAg levels of week 24 (RGT). For the subjects who qHBsAg\<200IU/ml of week 24, they are defined in Group A; the subjects in Group A will continue to be treated by NUC combined with PEG-IFN a-2a 180μg for another 24 weeks(total will be 48 weeks). If the qHBsAg at week 24 did not achieve minor 200IU/ml, the subjects will be randomized to 2 groups: Group B: the subjects will continue to be treated by NUC combined with PEG-IFN a-2a 180μg for another 24 weeks (total will be 48 weeks); Group C: the subjects will be treated by NUC until 48 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
324
Peginterferon alfa-2a 180μg /wk plus Entecavir 0.5mg qd for 48 weeks(Arm A and B)
Peginterferon alfa-2a 180μg /wk plus Lamivudine 0.1g qd for 48 weeks(Arm A and B)
Peginterferon alfa-2a 180μg /wk plus Adefovir 10mg qd for 48 weeks(Arm A and B)
Number of participants who achieve HBsAg clearance
To investigate whether HBsAg clearance rate can be improved at week 48 following applying RGT strategy(week 24) in NUC-experience subjects will be measured by the number of participants who achieve HBsAg clearance
Time frame: Week 48
Number of participants who achieve HBsAg seroconversion
To investigate the HBsAg seroconversion rate at week 48 can be improved following applying RGT strategy in NUC-experience subjects will be measured by the number of participants who achieve HBsAg seroconversion
Time frame: Week 48
Number of participants who achieve HBeAg loss
To investigate the HBeAg loss rate at week 48 can be improved following applying RGT strategy in NUC-experience subjects will be measured by the number of participants who achieve HBeAg loss
Time frame: Week 48
Number of participants who achieve HBeAg seroconversion
To investigate the HBeAg seroconversion rate at week 48 will be improved following applying RGT strategy in NUC-experience subjects will be measured by the number of participants who achieve HBeAg seroconversion
Time frame: Week 48
Percentage of of participants who achieve HBsAg decline >2log from baseline(0 week)
To investigate HBsAg decline from baseline at week 48 following applying RGT strategy in NUC-experience subjects by measured the percentage of of participants who achieve HBsAg decline\>2log from baseline(0 week)
Time frame: Week 48
Percentage of of participants who achieve HBsAg <10IU/mL
To investigate the percentage of of participants who achieve HBsAg \<100IU/mLat week 48 following applying RGT strategy in NUC-experience subjects
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Peginterferon alfa-2a 180μg /wk plus Tenofovir 300mg qd for 48 weeks(Arm A and B)
Entecavir 0.5mg qd for 24 weeks(Arm C)
Lamivudine 0.1g qd for 24 weeks(Arm C)
Adefovir 10mg qd for 24 weeks(ArmC)
Tenofovir 300mg qd for 24 weeks(Arm C)
Time frame: Week 48
Percentage of of participants who achieve combined response(defined as HBeAg seroconversion and HBVDNA<300copies/mL)
To investigate the percentage of of participants who achieve combined response at week 48 following applying RGT strategy in NUC-experience subjects will be measured by number of participants who achieve combined response
Time frame: Week 48
Percentage of of participants who achieve dural response I (defined as HBeAg seroconversion and HBsAg<100IU/mL)
To investigate the percentage of of participants who achieve dural response I at week 48 following applying RGT strategy in NUC-experience subjects will be measured by number of participants who achieve dural response
Time frame: Week 48
Percentage of of participants who achieve dural response II (defined as HBeAg seroconversion and HBsAg<10IU/mL)
To investigate the percentage of of participants who achieve dural response II at week 48 following applying RGT strategy in NUC-experience subjects will be measured by number of participants who achieve dural response
Time frame: Week 48
Number of participants who relapses (HBVDNA>1000copies/ml)
To investigate the number of participants who relapses following applying RGT strategy in NUC-experience subjects
Time frame: Week 48
Number of Participants with AE
Number of participants with adverse events as a measure of safety and tolerability
Time frame: Week 48
Number of Participants with SAE
Number of participants with SAEs as a measure of safety and tolerability
Time frame: Week 48