Safely Discontinue Antiviral Treatment in Patients With Chronic Hepatitis B (ADAPT)

A Multicenter Prospective Open-label Single Arm Trial to Safely Discontinue Antiviral Treatment in Patients With Chronic Hepatitis B With a Comparison to Matched Historical Controls (ADAPT)

Multicenter, Prospective Open-label Single Arm Trial Chronic hepatitis B male and female adults on antiviral treatment for hepatitis B, without cirrhosis who are currently HBV DNA (-) and HBeAg (-) To evaluate the safety and efficacy of stopping long-term antiviral therapy in chronic hepatitis B patients without cirrhosis who are currently HBV DNA (-) and HBeAg (-)

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Stop group

Detailed Description

This clinical trial is a multicenter, Prospective Open-label Single Arm Trial to compare the short-term clinical outcome between stopping and continuing antiviral treatment in chronic hepatitis B patients without cirrhosis who are currently HBV DNA (-) and HBeAg (-) Approximately 140 subjects meeting eligibility criteria will be enrolled a Intervention Arm as below;

• Intervention Arm: 140 subjects, discontinue antiviral treatment (stop group)
• Historical cohort: 700 subjects, continue antiviral treatment

Stop group is scheduled to be followed up to 6months. Patients in the stop group were retreated with nucleos(t)ide analogues that had been prescribed previously if they fulfill one of the following criteria: 1) HBV DNA >2,000 IU/mL, 2) progression to liver cirrhosis, or 3) development of hepatocellular carcinoma.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of
    • Kyungpook National University Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Chung-Ang University Hospital
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of
    • Konkuk University Hospital
  • Seoul, Korea, Republic of
    • Kyung-Hee University Hospital
  • Ulsan, Korea, Republic of
    • Ulsan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing and able to provide written informed consent prior to study entry
2. Age ≥19 years and ≤65 years at the time of screening
3. HBsAg titer <3,000 IU/mL at the time of screening
4. Antiviral treatment continued at least 2 years and HBeAg (-) at the time of screening
5. Undetectable HBV DNA level at the time of screening
6. Serum ALT level <80 IU/mL at the time of screening
7. Estimated creatinine clearance ≥30 ml/min (by calculation of creatinine clearance or using the CKD-EPI equation)
8. Ability to comply with all study requirements

Exclusion Criteria:

1. Confirmed known co-infection with HCV, HIV, or HDV
2. Evidence of liver cirrhosis defined as meeting any of the following criteria:
3. Current alcohol (60g/day) or substance abuse judged by the investigator that will potentially interfere with subject compliance (1) Splenomegaly (>12 cm) assessed by ultrasound, CT, or MRI (2) Fibroscan ≥9.0 kPa (3) Platelet count <150,000/mm3 However, if the above criteria were satisfied at the time of antiviral treatment initiation, subjects may be eligible if they have low possibility of having liver cirrhosis with improvement in liver function by long-term antiviral treatment, following the opinion of the investigator.
4. Any history of clinical hepatic decompensation (e.g., ascites, encephalopathy, variceal hemorrhage) within 12 months prior to the screening or Child-Pugh score of ≥7 at the time of screening
5. Currently on or have received therapy with Interferon or immunosuppressant (including systemic chemotherapy) within 12 months prior to the screening
6. Requirement for chronic use of systemic immunosuppressant including, but not limited to, corticosteroid (prednisone equivalent of >40 mg/day for >2 weeks), azathioprine, or monoclonal antibodies
7. Received solid organ or bone marrow transplant
8. Any other clinical conditions (cardiovascular, respiratory, neurologic, or renal conditions) or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements.
9. History or current evidence of hepatocellular carcinoma (HCC), or high α-fetoprotein (AFP) > 20 ng/mL. (But, the patients with AFP > 20 ng/mL can be enrolled and there is no evidence of HCC by dynamic CT or MRI perfomred within 4 months prior to the screening)
10. Malignancy other than hepatocellular carcinoma within the 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (within 2 years prior to screening with confirmation of no evidence of disease). Subjects under evaluation for possible malignancy are not eligible.
11. Concurrent enrollment in another clinical study for other type of antiviral treatment for CHB or immune modulatory drug within 3 months prior to Screening, participation to an observational (non-interventional) clinical studies or interventional studies not using anti-HBV or immune modulatory drugs, or during the follow-up period of an interventional study are not exclusion criteria.
12. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm A; discontinue antiviral treatment	Drug: Stop group; discontinue antiviral treatment; Other Names: discontinue antiviral treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
virological relapse	Proportion of virological relapse defined as HBV DNA ≥2,000 IU/mL	Change from baseline in HBV DNA result at 6month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hospital admission	Proportion of liver-related unexpected hospital admission	From baseline, clinical events will be collected within 6month
Proportion of clinical relapse	Proportion of clinical relapse (HBV DNA ≥2,000 IU/mL and ALT ≥80 IU/mL)	at 6 month

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Principal Investigator: Young-Suk Lim, PhD, Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 2, 2021
• First Submitted That Met QC Criteria: March 2, 2021
• First Posted (Actual): March 4, 2021

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Anti-Infective Agents; Antiviral Agents
• Other Study ID Numbers: AMC 2021-0135

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No