In short
A new clinical trial is exploring the potential of Tomligisiran, a novel drug, in combination with other medications for treating chronic hepatitis B (CHB). This study aims to assess the safety and effectiveness of a sequential therapy approach using Daplusiran/Tomligisiran (DAP/TOM) followed by Bepirovirsen in patients with CHB who are already on standard nucleos(t)ide analogue (NA) therapy. The trial seeks to determine the optimal dosage of DAP/TOM and evaluate its contribution to the overall treatment regimen.
At a glance
- Study Type
- Phase 2b, multi-center, randomized, partially placebo-controlled, double-blind
- Main Objective
- Evaluate efficacy and safety of DAP/TOM followed by Bepirovirsen in CHB patients
- Treatment Arms
- 5 arms based on HBsAg levels and DAP/TOM dosage
- Primary Outcome
- Number of participants achieving functional cure
- Secondary Outcomes
- Functional cure rates in high/low HBsAg groups, comparison with placebo
- Key Medications
- Daplusiran/Tomligisiran, Bepirovirsen, background NA therapy
- Treatment Stages
- DAP/TOM treatment, Bepirovirsen treatment, NA Only Stage, potential NA discontinuation
What is TOMLIGISIRAN?
TOMLIGISIRAN, also known as Daplusiran/Tomligisiran (DAP/TOM), is a new 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. This condition can lead to serious liver problems if left untreated.
How TOMLIGISIRAN Works
While the exact mechanism of action is not fully described in the provided information, TOMLIGISIRAN is being studied as part of a combination therapy with another drug called bepirovirsen. This combination approach suggests that TOMLIGISIRAN may work by targeting specific aspects of the hepatitis B virus lifecycle, potentially helping to reduce the virus's ability to replicate or survive in the body.
Clinical Trial Overview
A Phase 2b clinical trial, named B-United, is currently underway to investigate the safety and effectiveness of TOMLIGISIRAN in combination with bepirovirsen for treating chronic hepatitis B. This trial aims to:
- Evaluate the efficacy and safety of two different doses of TOMLIGISIRAN followed by bepirovirsen
- Identify the optimal dose of TOMLIGISIRAN for sequenced therapy with bepirovirsen
- Assess how TOMLIGISIRAN contributes to the overall treatment regimen
Participants in this study are people living with chronic hepatitis B who are already on standard nucleos(t)ide analogue (NA) therapy, which is a common treatment for hepatitis B.
Treatment Arms
The clinical trial is divided into several treatment arms, each testing different combinations and doses of the drugs:
- Treatment Arms 1A and 1B: For participants with high levels of hepatitis B surface antigen (HBsAg)
- 1A: TOMLIGISIRAN dose level 1 followed by bepirovirsen
- 1B: TOMLIGISIRAN dose level 2 followed by bepirovirsen
- Treatment Arms 2A, 2B, and 2C: For participants with low levels of HBsAg
- 2A: TOMLIGISIRAN dose level 1 followed by bepirovirsen
- 2B: TOMLIGISIRAN dose level 2 followed by bepirovirsen
- 2C: Placebo followed by bepirovirsen (control group)
All participants continue their background NA therapy throughout the treatment stages.
Expected Outcomes
The main goal of this study is to achieve what researchers call a "functional cure" for chronic hepatitis B. A functional cure is defined as:
- Sustained suppression of hepatitis B virus DNA (genetic material) below detectable levels for 24 weeks or longer after stopping all hepatitis B treatments
- Undetectable levels of hepatitis B surface antigen (HBsAg), with or without the presence of antibodies against HBsAg
The study will measure the number of participants achieving this functional cure in various groups, including those with high and low baseline HBsAg levels.
Potential Benefits
If successful, TOMLIGISIRAN in combination with bepirovirsen could offer several potential benefits for patients with chronic hepatitis B:
- A new treatment option that may lead to a functional cure, potentially allowing patients to stop long-term hepatitis B medications
- Improved suppression of the hepatitis B virus, reducing the risk of liver damage and other complications
- A treatment approach that may be effective for patients with different levels of hepatitis B surface antigen, potentially helping a wider range of patients
It's important to note that these potential benefits are still being studied, and more research is needed to confirm the safety and effectiveness of TOMLIGISIRAN.