The Hepatitis B e-Antigen Negative Disease - Directly Offered Study of Treatment Withdrawal in Patients With e-Antigen Negative Chronic HBV Infection (BeNEG-DO). (BeNEG-DO)

July 5, 2023 updated by: California Pacific Medical Center Research Institute

"BeNEG-DO": A Study of Clinical Outcomes, Immunologic Correlates and Genetic Predictors After Treatment Withdrawal in e-Antigen Negative (HBeAg-) Chronic Hepatitis B Virus (HBV) Infection

The investigators' research is aimed at developing more effective, finite approaches for managing individual patients with chronic hepatitis B (CHB). This prospective clinical and basic scientific study exclusively focuses on patients with the early antigen negative form of disease, which in developed countries is treated indefinitely with antiviral drugs. The investigators' study "BeNEG-DO," directly offers patients who are already taking standard oral Hepatitis B Virus (HBV) antiviral therapy for at least 192 weeks the option to stop or continue treatment. Drawing on data from pilot studies, including the investigators' own University of California, San Francisco and Sutter Institutional Review Board-approved study, the investigators will examine a finite HBV treatment strategy on clinical outcome and safety. In conjunction, the investigators will study immunologic mechanisms and gene expression profiles that correlate with and predict the post-treatment clinical course. The BeNEG-DO study could seriously question, and potentially change, the current treatment paradigm for millions of patients with CHB and also lead to new disease-terminating antiviral therapeutics.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

A prospective case-control study of safety and clinical outcomes, and of innate and adaptive immune responses and their genetic predictors, in adult human subjects with HBeAg-CHB who either continue or stop nucleoside or nucleotide analog (NA) antiviral therapy. Immune responses will be studied using liver tissue and serial peripheral blood samples. The immunological factors selected have been chosen based on preliminary and inferential evidence. Immunologic findings will be correlated with different serologic, virologic and biochemical outcomes. Genetic predictors of the type of response and respective clinical outcomes will also be sought.

Study Type

Interventional

Enrollment (Actual)

121

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • California Pacific Medical Center
      • San Francisco, California, United States, 94122
        • University of California, San Francisco

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 67 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. HBeAg-CHB with at least 192 weeks (3.7 years) of complete viral suppression (serum HBV DNA <50 IU/ml) on NA therapy
  2. No bridging fibrosis (≥ Metavir stage 3)
  3. Normal liver tests and platelet count
  4. Age 18-67
  5. Otherwise healthy with no serious co-morbidities
  6. Patients who are willing, prepared, and able to immediately resume antiviral treatment upon medical instruction and on satisfying study re-treatment criteria.

Exclusion Criteria:

  1. HBeAg-CHB with virologic breakthrough while on NA therapy during the prior 192 weeks (3.7 years)
  2. Age <18 or >67 years
  3. Significant co-morbidities including co-infection and significant co-existing liver disease or anemia. Mild Non-Alcoholic Fatty Liver Disease (NAFLD) without Non-Alcoholic Steatohepatitis (NASH) or associated liver enzyme elevation will be allowed.

  4. Bridging hepatic fibrosis (≥ Metavir stage 3) at the time of potential study entry

    a. Control Group: Determination will be based on historical biopsy data, imaging studies, Platelet count (<150,000), Aspartate aminotransferase to Platelet Ratio Index (APRI) <1.5) and Red Cell Distribution Width-to-Platelet Ratio (RPR) (<0.16) scores, and clinical assessment

  5. Alanine Aminotransferase (ALT) above the quoted normal range
  6. Clinical, serologic, radiological or biochemical suspicion for cirrhosis
  7. Prior liver transplantation
  8. A documented history of extrahepatic manifestations of hepatitis B, including renal disease and/or vasculitis
  9. Cases: A family history of hepatocellular carcinoma due to hepatitis B virus in a first degree family member
  10. On Prednisone or other immunosuppressive or immune-modulating therapy during the 6 months before study entry
  11. Pregnancy
  12. Patients who are not willing, prepared, and able to immediately resume antiviral treatment upon medical instruction and on satisfying re-treatment criteria

No one will be excluded on the basis of race, gender, religion, sexual orientation, or any cultural factor. An Institutional Review Board (IRB)-approved, translated consent will be used for patients that do not speak English

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HBeAg-CHB patients who stop NA Therapy

Patients with early antigen negative form of disease (HBeAg-CHB) who are already taking standard oral HBV antiviral therapy for at least 192 weeks that stop treatment.

Intervention: Cases will stop antiviral therapy
Other: Stop NA therapy
Cases will stop antiviral therapy
No Intervention: HBeAg-CHB patients continue NA Therapy

Patients with early antigen negative form of disease (HBeAg-CHB) who are already taking standard oral HBV antiviral therapy for at least 192 weeks that continue to stay on treatment.

Intervention: None. Controls will continue antiviral therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serologic response and rate: HBsAg persistence versus loss; HBsAb production (+/-). This clinically relevant endpoint evaluates chronic HBV clearance and persistence
Time Frame: 10 years
Annual seroclearance rates of 0.5%-0.8% in controls are assumed (American Association for the Study of Liver Diseases 2012 Poster 374) and equivalent to the estimated spontaneous rate (Hepatology 2009; 49:S45-55). In cases, 5-6% (based on Gastroenterology 2012 143:629:636) 5 year rates for HBsAg seroconversion (5%) or HBsAg loss only.
10 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Liver biochemical response: ALT level
Time Frame: 5 years
These anticipated biochemical outcomes are based on Gastroenterology 2012 143:629-636
5 years
Virologic response: HBV DNA level
Time Frame: 10 years
Hepatitis B Virus levels measured in International Units per milliliter
10 years
Case retreatment rate
Time Frame: 10 years
As a measure of safety
10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

California Pacific Medical Center Research Institute

Collaborators

University of California, San Francisco

Investigators

  • Principal Investigator: Stewart L Cooper, MD, Sutter Health - California Pacific Medical Center
  • Principal Investigator: Jody L Baron, MD, PhD, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 17, 2016

Primary Completion (Estimated)

May 25, 2026

Study Completion (Estimated)

May 31, 2026

Study Registration Dates

First Submitted

July 21, 2016

First Submitted That Met QC Criteria

July 22, 2016

First Posted (Estimated)

July 27, 2016

Study Record Updates

Last Update Posted (Actual)

July 7, 2023

Last Update Submitted That Met QC Criteria

July 5, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1R01DK103735-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chronic Hepatitis B Virus

Clinical Trials on Stop NA therapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Tanzania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe