Biomarkers Guided Stopping NAs Treatment

Chronic Hepatitis b Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04519359
• Other study ID #: STOP-01
• Status: Recruiting
• Phase: N/A
• Start date: July 6, 2020
• Est. completion date: June 30, 2023

Study information

• Verified date: August 2020
• Source: Nanfang Hospital of Southern Medical University
• Contact: Jian Sun, MD
• Phone: 86-20-62787432
• Email: doctorsunjian[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 195
• Est. completion date: June 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis b
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Other:
• Stop NAs therapy
Stop NAs therapy

Locations

Country	Name	City	State
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	No. 1 Hospital affiliated to Jilin University	Chang chun	Jilin
China	Ruijin Hospital	Shanghai	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning

Sponsors (1)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants With HBsAg Loss at Week 72 in Both Study Arms	HBsAg loss is defined as qualitative HBsAg result changing from positive at baseline (BL) to negative at any post-baseline visit. Proportions are based on a Kaplan-Meier estimate.	Week 72
Secondary	Proportion of Participants With Sustained Disease Remission at Week 72 in Both Study Arms	Sustained Disease Remission is defined as HBeAg negativity, HBV DNA <2000 IU/mL and ALT normalization at any post-baseline visit. Proportions are based on a Kaplan-Meier estimate.	Week 72
Secondary	Proportion of Participants With Clinical Relapse at Week 72 in Both Study Arms	Clinical Relapse is defined as HBV DNA >2000 IU/mL and ALT >2 ULN at any post-baseline visit. Proportions are based on a Kaplan-Meier estimate.	Week 72
Secondary	Proportion of Participants With Virologic Relapse at Week 72 in Both Study Arms	Virologic Relapse is defined as HBV DNA >2000 IU/mL at two consecutive timepoints [at least 14 days apart] at any post-baseline visit. Proportions are based on a Kaplan-Meier estimate.	Week 72
Secondary	Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms	The analyses were summarized by 3 treatment subgroups: Stop NAs (NAs-Free), Restart NAs, and Continue NAs When participant randomized in the Stop NAs group restarted NAs therapy, that participant was considered part of the Restart NAs group from that point forward. For Restart NAs group, baseline is defined as the last available record on or prior to the restart date of NAs.	Week 72