NCT03681132

The Norwegian Nucleoside Analogue Stop Study

The Norwegian Nucleoside Analogue Stop Study: a Randomized Open-label Trial in HBeAg Negative Chronic Hepatitis B, Aiming at Achieving a Functional Cure.

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 127 (actual)
• Sponsor: Oslo University Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Globally, an estimated 257 million individuals have chronic hepatitis B-virus infection (CHB). In the absence of treatment 15-40% of these will progress to liver cirrhosis and/or hepatocellular carcinoma. Oral antiviral treatment suppresses the virus and improves prognosis, but less than 0.5% per year achieve a "functional cure" (i.e. HBsAg loss). One remaining controversy, therefore, is whether antiviral treatment must continue life-long. Observational studies have assessed stopping antiviral treatment after years of viral suppression; however, HBsAg loss has rarely been seen. But interestingly, a few small trials that chose watchful waiting instead of re-initiation of treatment when reactivation occurred, achieved 40% HBsAg loss during 6 years follow-up. The present proposal is a randomized controlled trial that will assess the safety, efficacy, and cost-effectiveness of treatment discontinuation - and delayed restart - in HBeAg negative CHB. The study is sufficiently powered to address the hypotheses, and a pilot study that demonstrates feasibility has been performed. Patients will be enrolled at 12 Norwegian hospitals, in addition to our collaborating institution in Ethiopia - the largest CHB treatment center in sub-Saharan Africa. If the study shows that discontinuation is safe and effective, it will directly impact both national and international treatment guidelines. Main objective: -To study whether stopping nucleoside analogue (NA) therapy - and delaying re-start - can trigger an immune response and set off a functional cure (viz HBsAg loss) Secondary objectives: * Assess whether stopping NA therapy - and delaying re-start - leads to a higher chance of HBsAg loss * Assess the safety of stopping NA therapy - and delaying re-start - in terms of hepatic decompensation, fibrosis progression, and/or adverse events * Study whether stopping NA therapy - and delaying re-start - leads to a higher chance of sustained off-therapy immune control (low viral load and normal ALT) * Assess the quality of life and cost-effectiveness of stopping NA therapy - and delaying re-start * Identify predictors of HBsAg loss

Conditions

• Hepatitis B, Chronic

Interventions

Type	Name	Description
OTHER	Stop of therapy	The active intervention is to stop antiviral therapy, and delay re-start in the high-threshold group.

Timeline

• Start date: 2018-09-20
• Primary completion: 2023-01-31
• Completion: 2023-01-31
• First posted: 2018-09-21
• Last updated: 2023-03-20

Locations

11 sites across 4 countries: Denmark, Ethiopia, Norway, Sweden