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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)

Primary Purpose

Chronic Hepatitis B Virus

Status

Active

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Stop NA therapy

About this trial

This is an interventional basic science trial for Chronic Hepatitis B Virus focused on measuring Viral, Hepatitis

Eligibility Criteria

18 Years - 67 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

HBeAg-CHB with virologic breakthrough while on NA therapy during the prior 192 weeks (3.7 years)
Age <18 or >67 years
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.
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
Alanine Aminotransferase (ALT) above the quoted normal range
Clinical, serologic, radiological or biochemical suspicion for cirrhosis
Prior liver transplantation
A documented history of extrahepatic manifestations of hepatitis B, including renal disease and/or vasculitis
Cases: A family history of hepatocellular carcinoma due to hepatitis B virus in a first degree family member
On Prednisone or other immunosuppressive or immune-modulating therapy during the 6 months before study entry
Pregnancy
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

Sites / Locations

California Pacific Medical Center
University of California, San Francisco

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

HBeAg-CHB patients who stop NA Therapy

HBeAg-CHB patients continue NA Therapy

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Serologic response and rate: HBsAg persistence versus loss; HBsAb production (+/-). This clinically relevant endpoint evaluates chronic HBV clearance and persistence

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.

Secondary Outcome Measures

Liver biochemical response: ALT level

These anticipated biochemical outcomes are based on Gastroenterology 2012 143:629-636

Virologic response: HBV DNA level

Hepatitis B Virus levels measured in International Units per milliliter

Case retreatment rate

As a measure of safety

Full Information

NCT ID

NCT02845401

First Posted

July 21, 2016

Last Updated

July 5, 2023

Sponsor

California Pacific Medical Center Research Institute

Collaborators

University of California, San Francisco

1. Study Identification

Unique Protocol Identification Number

NCT02845401

Brief Title

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

Acronym

BeNEG-DO

Official Title

"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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

November 17, 2016 (Actual)

Primary Completion Date

May 25, 2026 (Anticipated)

Study Completion Date

May 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

California Pacific Medical Center Research Institute

Collaborators

University of California, San Francisco

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

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

Chronic Hepatitis B Virus

Keywords

Viral, Hepatitis

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Investigator

Allocation

Non-Randomized

Enrollment

121 (Actual)

8. Arms, Groups, and Interventions

Arm Title

HBeAg-CHB patients who stop NA Therapy

Arm Type

Experimental

Arm Description

Arm Title

HBeAg-CHB patients continue NA Therapy

Arm Type

No Intervention

Arm Description

Intervention Type

Other

Intervention Name(s)

Stop NA therapy

Intervention Description

Cases will stop antiviral therapy

Primary Outcome Measure Information:

Title

Serologic response and rate: HBsAg persistence versus loss; HBsAb production (+/-). This clinically relevant endpoint evaluates chronic HBV clearance and persistence

Description

Time Frame

10 years

Secondary Outcome Measure Information:

Title

Liver biochemical response: ALT level

Description

These anticipated biochemical outcomes are based on Gastroenterology 2012 143:629-636

Time Frame

5 years

Title

Virologic response: HBV DNA level

Description

Hepatitis B Virus levels measured in International Units per milliliter

Time Frame

10 years

Title

Case retreatment rate

Description

As a measure of safety

Time Frame

10 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

67 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: HBeAg-CHB with at least 192 weeks (3.7 years) of complete viral suppression (serum HBV DNA <50 IU/ml) on NA therapy No bridging fibrosis (≥ Metavir stage 3) Normal liver tests and platelet count Age 18-67 Otherwise healthy with no serious co-morbidities Patients who are willing, prepared, and able to immediately resume antiviral treatment upon medical instruction and on satisfying study re-treatment criteria. Exclusion Criteria: HBeAg-CHB with virologic breakthrough while on NA therapy during the prior 192 weeks (3.7 years) Age <18 or >67 years 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. 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 Alanine Aminotransferase (ALT) above the quoted normal range Clinical, serologic, radiological or biochemical suspicion for cirrhosis Prior liver transplantation A documented history of extrahepatic manifestations of hepatitis B, including renal disease and/or vasculitis Cases: A family history of hepatocellular carcinoma due to hepatitis B virus in a first degree family member On Prednisone or other immunosuppressive or immune-modulating therapy during the 6 months before study entry Pregnancy 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stewart L Cooper, MD

Organizational Affiliation

Sutter Health - California Pacific Medical Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jody L Baron, MD, PhD

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

California Pacific Medical Center

City

San Francisco

State/Province

California

ZIP/Postal Code

94115

Country

United States

Facility Name

University of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94122

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

Learn more about this trial

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

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