Clinical Trials in Chronic Hepatitis B Look To Optimize Dose, Regimen For Tolerable Immune Activation

Chronic hepatitis B virus (HBV) infection affects about 296 million people globally and is the leading worldwide cause of cirrhosis and liver cancer. The World Health Organization’s global hepatitis strategy, endorsed by all WHO Member States, aims to reduce new hepatitis infections by 90% and deaths by 65% between 2016 and 2030.2 However, annual global deaths from HBV are projected to increase by 39% from 2015 to 2030 if the status quo remains.1

This blog reviews several clinical trials of new HBV treatments and discusses how researchers are working to balance safety, dose, and regimen to promote immune activation.3

Long-term administration of nucleos(t)ide analogues (NA) has been the treatment of choice for chronic hepatitis B in recent decades.4 Although efficient in reducing HBV replication and liver inflammation in patients with HBV, the NA therapies rarely achieve a functional cure.5 In recent years, greater knowledge about the viral cycle and immunologic insights have yielded an increase in new HBV therapeutic approaches. New therapies that not only inhibit viral replication but stimulate antiviral immunity are being developed.6 Toll-like receptors TLR-7, TLR-8, TLR-9, and retinoic acid–inducible gene 1 (RIG-I) agonists are the major representatives of this dual-acting class of immune therapies.7 Researchers working on these agents continue to make progress in optimizing dose and regimen to provide tolerable immune activation.

Hepatitis B trial achieves 97.8% adherence in complex regimen

One sponsor looking to find this balance with a TLR agonist used AiCure medication adherence technology in a phase I study in healthy volunteers and in patients with chronic HBV infection. Due to COVID-19, the study was unable to be performed in clinic; researchers therefore deployed AiCure on patient smartphones to remotely assess compliance in their own homes with a complex dosing regimen requiring up to 5 pills per day. AiCure trained computer vision models to ensure participants received the appropriate dose. With this dosing support, participants achieved a notably high 97.8% compliance rate and contributed to positive results that moved the drug into phase II. Learn more by downloading the case study.

The emerging strategy for using TLR-7 agonists as therapeutic agents for chronic HBV involves the use of these agents to stimulate immune activation in combination with a direct acting antiviral agent.5 By providing novel analysis of dosing behaviors linked to patient-reported outcomes, AiCure technology may help with the challenge of picking the optimal dose and regimen for these agents.Read the AiCure Patient Connect fact sheet to learn more.

1 Global burden of hepatitis B virus: current status, missed opportunities and a call for action | Nature Reviews Gastroenterology & Hepatology
2 Elimination of hepatitis by 2030, Health Topics, World Health Organization, accessed 12 July 2023
3 Content powered by Perplexity AI
4 Past, present, and future of long-term treatment for hepatitis B virus
5 Fine‐Tuning TLR‐7‐Based Therapy for Functional HBV Cure - PMC
6 Ibid
7 Ibid