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

NCT02845401 | Active Not Recruiting DMC

• 1 other identifier: 1R01DK103735-01A1
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 2

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.

Conditions

Chronic Hepatitis B Virus

Keywords

Viral; Hepatitis

Outcome Measures

Primary Outcomes (1)

• 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.

  10 years

Secondary Outcomes (3)

• Liver biochemical response: ALT level

  5 years

• Virologic response: HBV DNA level

  10 years

• Case retreatment rate

  10 years

Study Arms (2)

HBeAg-CHB patients who stop NA Therapy

EXPERIMENTAL

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

HBeAg-CHB patients continue NA Therapy

NO INTERVENTION

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.

Interventions

Stop NA therapy OTHER

Cases will stop antiviral therapy

HBeAg-CHB patients who stop NA Therapy

Eligibility Criteria

• Age: 18 Years - 67 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• California Pacific Medical Center Research Institute: lead
• University of California, San Francisco: collaborator

Study Sites (2)

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of California, San Francisco

San Francisco, California, 94122, United States

Location

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stewart L Cooper, MD

  Sutter Health - California Pacific Medical Center

  PRINCIPAL INVESTIGATOR

• Jody L Baron, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2016
• First Posted: July 27, 2016
• Study Start: November 17, 2016
• Primary Completion (Estimated): May 25, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: July 7, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share

Locations

US (2)