Biomarkers Guided Stopping NAs Treatment

Novel Biomarkers Guided Stopping Nucleos(t)Ide Analogues After Long-term Virologic Suppression in CHB Patients: a Randomized Control Trial

The primary objective of this study is to evaluate hepatitis B surface antigen (HBsAg) loss in subjects who stop nucles(t)ide analogues (NAs) (Stop arm) compared to subjects who continue (Continue arm) Only subjects who already are on treatment with ETV, TDF or TAF monotherapy, and have achieved sustained virologic suppression (<20 IU/mL), HBeAg negativity, normal ALT for more than 1 year (pretreatment HBeAg + pts) or 3 years (pretreatment HBeAg - pts), plus qHBsAg <200 IU/mL, and HBV RNA or HBcrAg negativity will be included in this study. One treatment arm will stop the NAs therapy while the other treatment arm will continue the NAs therapy. Participants in the Stop arm will be monitored very closely with special focus on clinical relapse. If any participant in the Stop NAs arm exceeds one or more predefined limits for such flares or relapses, NAs treatment will be reinstituted.

Key Inclusion Criteria:

• 18-65 years of old, male or female
• Chronic hepatitis B patients
• Received continuous ETV, TDF or TAF therapy for at least 1 year prior to screening and at screening
• For patients with Hepatitis B e Antigen (HBeAg)-positive at the beginning of NAs therapy, documented hepatitis B virus <20 IU/mL, HBeAg seroconversion and ALT normalization for at least 1 year prior to screening and at screening
• For patients with HBeAg-negative at the beginning of NAs therapy, documented hepatitis B virus <20 IU/mL, and ALT normalization for at least 3 year prior to screening and at screening
• <= 9 kPa on Fibroscan assessment
• qHBsAg <200 IU/mL within 24 weeks prior to screening
• HBV RNA or HBcrAg negativity within 24 weeks prior to screening

Key Exclusion Criteria:

• Experience of IFN treatment within 1 year prior to screening
• Known cirrhosis
• History of decompensated liver disease
• History of clinical hepatic decompensation in the judgement of the investigator
• Evidence of hepatocellular carcinoma
• Serological evidence of coinfection with human immunodeficiency virus (HIV), hepatitis C virus, or hepatitis D infection
• Known hypersensitivity to TDF, its metabolites, or formulation excipients
• History of malignant disease
• Lactating females
• Females wishing to became pregnant during the duration of the study
• Subjects participating in another clinical trial