Stopping Antiviral Therapy for Chronic Hepatitis B

(BeNEG-DO Trial)

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: California Pacific Medical Center Research Institute

Must be taking: Antivirals

Must not be taking: Immunosuppressants

Disqualifiers: Co-infection, Liver disease, Anemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if stopping antiviral drugs is safe and effective for patients with chronic hepatitis B (CHB) after at least 3.7 years of use. Researchers seek better and potentially shorter treatment plans for those with an early antigen-negative form of the disease, typically treated indefinitely. Participants will either stop their medication ("Stop NA therapy") to observe health progression or continue their current treatment for comparison. Ideal candidates have stable CHB, no significant liver damage, and normal liver function tests while on medication. As an unphased trial, this study allows patients to contribute to groundbreaking research that could lead to more effective treatment plans.

Will I have to stop taking my current medications?

The trial specifically allows participants to stop their current antiviral therapy for chronic hepatitis B if they choose, as long as they have been on the treatment for at least 192 weeks. Participants must be ready to restart the medication if needed, based on medical advice.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that stopping nucleos(t)ide analog (NA) therapy for chronic hepatitis B (CHB) can be safe for some patients. In one study of 1,552 patients who stopped their NA treatment, 3.2% lost the hepatitis B surface antigen (HBsAg) after one year, indicating improved health.

The chance of the disease returning, known as the relapse rate, is important to consider. Another study found a risk of relapse after stopping treatment, but this risk varies based on individual health and treatment effectiveness.

Patients who stop NA therapy may also face a lower risk of liver cancer and liver disease. A meta-analysis, which combined results from several studies, showed a 70% reduction in liver cancer and a 72% reduction in liver disease after stopping therapy.

These findings suggest that stopping NA therapy can be a safe option for some patients. However, discussing personal health with a doctor is crucial to determine if this is the right choice. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for chronic Hepatitis B involve long-term antiviral therapy to keep the virus in check. But researchers are excited about the potential to stop nucleos(t)ide analogue (NA) therapy for some patients. This approach is unique because it explores the possibility of maintaining health and virus suppression without continuous medication. If successful, it could reduce the burden of lifelong treatment, decrease side effects, and improve quality of life for patients.

What evidence suggests that stopping NA therapy might be an effective treatment for chronic hepatitis B?

In this trial, participants with chronic hepatitis B (CHB) will be divided into two groups: one will continue nucleos(t)ide analog (NA) therapy, while the other will stop it. Research has shown that stopping NA therapy can lead to mixed outcomes. Some studies indicate that about 3-4% of those who stop treatment lose HBsAg, a marker of the virus in the blood. However, this benefit is limited, and stopping treatment can sometimes cause serious liver problems for a small number of patients. Specifically, another study found that some patients experienced liver-related issues after stopping therapy. Overall, the results of stopping NA therapy vary and come with potential risks, so the decision should be made carefully. ^{1 2 4 6 7}

Who Is on the Research Team?

Stewart Cooper, Dr.

Principal Investigator

Sutter Health - California Pacific Medical Center

Jody L Baron, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults aged 18-67 with e-Antigen negative chronic Hepatitis B who've been on antiviral therapy for at least 3.7 years, have no serious liver damage or other major health issues, and can restart treatment if needed. It's not for those with advanced liver fibrosis, abnormal liver tests, cirrhosis suspicion, prior transplants, recent immunosuppressive therapy use, pregnancy or significant co-morbidities.

Inclusion Criteria

I am generally healthy with no serious health issues.

I am ready to restart antiviral treatment when told by a doctor.

No bridging fibrosis (≥ Metavir stage 3)

Exclusion Criteria

I have hepatitis B and my treatment in the last 3.7 years hasn't stopped the virus.

I have had kidney problems or blood vessel inflammation due to hepatitis B.

A close family member had liver cancer due to hepatitis B.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Withdrawal

Participants who have been on antiviral therapy for at least 192 weeks either stop or continue treatment

192 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment withdrawal

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Stop NA therapy

Trial Overview The BeNEG-DO study offers patients the choice to stop or continue their ongoing oral HBV antiviral treatment after a minimum of 192 weeks. The aim is to assess the effects of ending treatment on clinical outcomes and safety while exploring immune responses and genetic markers that may predict post-treatment results.

How Is the Trial Designed?

Group I: HBeAg-CHB patients who stop NA Therapy Experimental Treatment 1 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 stop treatment. Intervention: Cases will stop antiviral therapy

Group II: HBeAg-CHB patients continue NA Therapy Active Control 1 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.

Who Is Running the Clinical Trial?

California Pacific Medical Center Research Institute

Lead Sponsor

Trials

44

Recruited

10,600+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31462554/

results from a randomised controlled trial (Toronto STOP ... Conclusion: The findings of this prospective study suggest limited benefit of stopping NA therapy in chronic hepatitis B. Trial registration number ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772572324001304

Nucleos(t)ide Analog Treatment Discontinuation in Chronic ... HBsAg loss was observed in 4% of patients who stopped NA therapy (maximum follow-up of 48 weeks); lower levels of HBcrAg and HBsAg were associated with improved ...

3. cghjournal.org cghjournal.org/article/S1542-3565(24)00516-0/fulltext

Stopping Nucleos(t)ide Analogues in Chronic Hepatitis B ... Subsequent meta-analyses have reported variable HBsAg loss rates of 1.7%–27%, in those stopping NA therapy but with little information about ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5900846/

Stopping nucleos(t)ide analogue treatment in Caucasian ... Treatment cessation led to liver‐related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg ...

5. gastrojournal.org gastrojournal.org/article/S0016-5085(21)03723-9/fulltext

Off-Therapy Response After Nucleos(t)ide Analogue ... In this study of 1552 patients with CHB who stopped NA therapy, the cumulative probability of HBsAg loss at year 1 of follow-up was 3.2%, which more than ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4367206/

Outcome after discontinuation of nucleot(s)ide analogues ... This article reviews the relapse rate after cessation of treatment with NAs in chronic hepatitis B patients with the goal of identifying possible predictive ...

7. idcmjournal.org idcmjournal.org/nucleostide-analogues-in-the-long-way-stop-or-continue

Discontinuation of Nucleos(t)ide Analogues in HBeAg ... Patients with HBeAg-negative Chronic hepatitis B (CHB) who have a higher chance of response after discontinuation of NA therapy can be defined ...