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Biomarkers Guided Stopping NAs Treatment

Primary Purpose

Chronic Hepatitis b

Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Stop NAs therapy
Sponsored by
Nanfang Hospital, Southern Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Chronic Hepatitis b

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Beijing Friendship Hospital, Capital Medical UniversityRecruiting
  • Peking University People's HospitalRecruiting
  • No. 1 Hospital affiliated to Jilin UniversityRecruiting
  • Shengjing Hospital of China Medical UniversityRecruiting
  • Ruijin HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Stop Arm

Continue Arm

Arm Description

Stop NAs therapy

Continue NAs therapy

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
August 17, 2020
Last Updated
August 17, 2020
Sponsor
Nanfang Hospital, Southern Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT04519359
Brief Title
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

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Unknown status
Study Start Date
July 6, 2020 (Actual)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
June 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nanfang Hospital, Southern Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis b

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
195 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Stop Arm
Arm Type
Experimental
Arm Description
Stop NAs therapy
Arm Title
Continue Arm
Arm Type
No Intervention
Arm Description
Continue NAs therapy
Intervention Type
Other
Intervention Name(s)
Stop NAs therapy
Intervention Description
Stop NAs therapy
Primary Outcome Measure Information:
Title
Proportion of Participants With HBsAg Loss at Week 72 in Both Study Arms
Description
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.
Time Frame
Week 72
Secondary Outcome Measure Information:
Title
Proportion of Participants With Sustained Disease Remission at Week 72 in Both Study Arms
Description
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.
Time Frame
Week 72
Title
Proportion of Participants With Clinical Relapse at Week 72 in Both Study Arms
Description
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.
Time Frame
Week 72
Title
Proportion of Participants With Virologic Relapse at Week 72 in Both Study Arms
Description
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.
Time Frame
Week 72
Title
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms
Description
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.
Time Frame
Week 72

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jian Sun, MD
Phone
86-20-62787432
Email
doctorsunjian@qq.com
Facility Information:
Facility Name
Beijing Friendship Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hong Ma, MD
Email
mahongmd@aliyun.com
Facility Name
Peking University People's Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Huiying Rao, MD
Email
rao.huiying@163.com
Facility Name
No. 1 Hospital affiliated to Jilin University
City
Chang chun
State/Province
Jilin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yanhang Gao, MD
Email
gyhd0165@163.com
Facility Name
Shengjing Hospital of China Medical University
City
Shenyang
State/Province
Liaoning
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaoguang Dou, MD
Email
guang40@163.com
Facility Name
Ruijin Hospital
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qing Xie, MD
Email
xieqingrjh@163.com

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Biomarkers Guided Stopping NAs Treatment

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