ADAPT: Safely Discontinue Antiviral Treatment in Patients With Chronic Hepatitis B

• Sponsor: Asan Medical Center (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04782375
• Collaborator: (none)
• Enrollment: 140
• Locations: 10
• Arm: 1
• Anticipated Duration (Months): 39
• Patients Per Site: 14
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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 (-)

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Drug: Stop group	Phase 4

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: 140 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 Design

• Study Type: Interventional
• Anticipated Enrollment: 140 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: 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)
• Actual Study Start Date: Sep 1, 2021
• Anticipated Primary Completion Date: Jun 1, 2024
• Anticipated Study Completion Date: Dec 1, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. virological relapse [Change from baseline in HBV DNA result at 6month]

   Proportion of virological relapse defined as HBV DNA ≥2,000 IU/mL

Secondary Outcome Measures

1. hospital admission [From baseline, clinical events will be collected within 6month]

   Proportion of liver-related unexpected hospital admission

2. Proportion of clinical relapse [at 6 month]

   Proportion of clinical relapse (HBV DNA ≥2,000 IU/mL and ALT ≥80 IU/mL)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 <40 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 including 2-month visit interval

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, or current evidence of, clinical hepatic decompensation (e.g., ascites, encephalopathy, variceal hemorrhage, 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 if AFP shows decreasing trend and there is no evidence of HCC by dynamic CT or MRI)

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 randomization, 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kyungpook National University Hospital	Daegu		Korea, Republic of
2	Asan Medical Center	Seoul		Korea, Republic of
3	Chung-Ang University Hospital	Seoul		Korea, Republic of
4	Konkuk University Hospital	Seoul		Korea, Republic of
5	Korea University Guro Hospital	Seoul		Korea, Republic of
6	Kyung-Hee University Hospital	Seoul		Korea, Republic of
7	Samsung Medical center	Seoul		Korea, Republic of
8	Seoul National University Hospital	Seoul		Korea, Republic of
9	Seoul St. Mary's Hospital	Seoul		Korea, Republic of
10	Ulsan University Hospital	Ulsan		Korea, Republic of

Sponsors and Collaborators

• Asan Medical Center

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Young-Suk Lim, PhD, Asan Medical Center
• ClinicalTrials.gov Identifier: NCT04782375
• Other Study ID Numbers: AMC 2021-0135
• First Posted: Mar 4, 2021
• Last Update Posted: May 17, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Antiviral Agents

Study Results

No Results Posted as of May 17, 2022