Clinical trial NCT04519359: Biomarkers Guided Stopping NAs Treatment
Official title: Novel Biomarkers Guided Stopping Nucleos(t)Ide Analogues After Long-term Virologic Suppression in CHB Patients: a Randomized Control Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Chronic Hepatitis b
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2020-08-19
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Participants With HBsAg Loss at Week 72 in Both Study Arms
timeFrame: Week 72
Secondary outcomes:
measure: Proportion of Participants With Sustained Disease Remission at Week 72 in Both Study Arms
timeFrame: Week 72
measure: Proportion of Participants With Clinical Relapse at Week 72 in Both Study Arms
timeFrame: Week 72
measure: Proportion of Participants With Virologic Relapse at Week 72 in Both Study Arms
timeFrame: Week 72
measure: Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms
timeFrame: Week 72
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Chang chun
country: China
facility: No. 1 Hospital affiliated to Jilin University
state: Jilin
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Ruijin Hospital
state: Shanghai
Study officials:
References: