In short
This article explores an ongoing clinical trial investigating the use of Daplusiran/Tomligisiran (DAP/TOM) followed by Bepirovirsen in treating chronic hepatitis B (CHB). The study aims to assess the safety and effectiveness of this sequential therapy in patients already receiving standard nucleos(t)ide analogue (NA) treatment. The trial's primary goal is to determine the optimal dosage of DAP/TOM when used in combination with Bepirovirsen and to evaluate its contribution to the overall treatment regimen.
At a glance
- Study Type
- Phase 2b, multi-center, randomized, partially placebo-controlled, double-blind study
- Condition
- Chronic Hepatitis B Virus Infection
- Interventions
- Daplusiran/Tomligisiran (two dose levels), Bepirovirsen, Placebo
- Treatment Arms
- 5 arms based on HBsAg levels and drug combinations
- Primary Outcome
- Number of participants achieving functional cure
- Secondary Outcomes
- Functional cure rates in different subgroups, HBsAg and HBV DNA suppression
- Treatment Stages
- DAP/TOM or Placebo, followed by Bepirovirsen, then observation on NA, and potential NA discontinuation
What is Daplusiran?
Daplusiran, also known as DAP/TOM (Daplusiran/Tomligisiran), is a new investigational drug being studied for the treatment of chronic hepatitis B virus (CHB) infection. Chronic hepatitis B is a long-lasting liver infection caused by the hepatitis B virus, which can lead to serious liver problems if left untreated.
How Daplusiran Works
While the exact mechanism of action is not fully described in the provided information, Daplusiran is being studied as part of a sequential therapy approach. This means it is used in combination with other medications to potentially improve the treatment outcomes for patients with chronic hepatitis B.
Clinical Trial Overview
A Phase 2b clinical trial, called B-United, is currently underway to investigate the safety and effectiveness of Daplusiran. This trial is designed to evaluate different doses of Daplusiran followed by another drug called bepirovirsen in patients with chronic hepatitis B who are already on standard nucleos(t)ide analogue (NA) therapy.
The main goals of this study are:
- To assess how well Daplusiran works in combination with bepirovirsen
- To determine the best dose of Daplusiran for future clinical development
- To understand how Daplusiran contributes to the overall treatment regimen
Treatment Arms and Dosing
The clinical trial includes several treatment arms, which are different groups of patients receiving various combinations of medications. These arms are divided based on the patients' initial levels of hepatitis B surface antigen (HBsAg), a protein found on the surface of the hepatitis B virus that indicates active infection.
The treatment arms include:
- High HBsAg level groups:
- Treatment Arm 1A: Daplusiran/Tomligisiran Dose Level 1 + Bepirovirsen
- Treatment Arm 1B: Daplusiran/Tomligisiran Dose Level 2 + Bepirovirsen
- Low HBsAg level groups:
- Treatment Arm 2A: Daplusiran/Tomligisiran Dose Level 1 + Bepirovirsen
- Treatment Arm 2B: Daplusiran/Tomligisiran Dose Level 2 + Bepirovirsen
- Treatment Arm 2C: Placebo + Bepirovirsen (control group)
All participants will continue their background nucleos(t)ide analogue therapy throughout the treatment stages.
Expected Outcomes
The primary goal of this study is to achieve a functional cure for chronic hepatitis B. A functional cure is defined as:
- Sustained suppression (24 weeks or longer) of hepatitis B virus DNA below detectable levels
- Undetectable hepatitis B surface antigen (HBsAg)
- These results should be maintained after stopping all hepatitis B treatments
The study will measure the number of participants achieving a functional cure in various scenarios, including:
- Overall functional cure rate
- Functional cure rate in patients with high initial HBsAg levels
- Functional cure rate in patients with low initial HBsAg levels
- Comparison of functional cure rates between Daplusiran-treated groups and the placebo group (for low HBsAg patients)
Potential Benefits for Patients
If successful, this new treatment approach using Daplusiran could offer several potential benefits for patients with chronic hepatitis B:
- Improved chances of achieving a functional cure, which means long-term control of the hepatitis B virus without ongoing medication
- Possibility of stopping all hepatitis B treatments after a finite duration of therapy
- Potential for better outcomes compared to current standard treatments alone
- A new option for patients who may not have responded well to other therapies
It's important to note that Daplusiran is still in the investigational stage, and more research is needed to fully understand its effectiveness and safety profile. Patients interested in this treatment should consult with their healthcare providers about the possibility of participating in clinical trials or when this medication might become available for general use.