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Daplusiran

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.

Table of Contents

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[1]. 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[1].

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[1].

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[1].

The treatment arms include:

  1. High HBsAg level groups:
    • Treatment Arm 1A: Daplusiran/Tomligisiran Dose Level 1 + Bepirovirsen
    • Treatment Arm 1B: Daplusiran/Tomligisiran Dose Level 2 + Bepirovirsen
  2. 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[1].

Expected Outcomes

The primary goal of this study is to achieve a functional cure for chronic hepatitis B. A functional cure is defined as[1]:

  • 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[1]:

  • 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[1]:

  • 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.

Aspect Details
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

FAQ

  • What is the main purpose of this clinical trial? The main purpose of this clinical trial is to evaluate the efficacy and safety of two different doses of Daplusiran/Tomligisiran (DAP/TOM) followed by Bepirovirsen in people living with chronic hepatitis B who are already on standard nucleos(t)ide analogue (NA) therapy. The study also aims to identify the best dose of DAP/TOM for use in combination with Bepirovirsen for future clinical development.
  • Who can participate in this trial? The trial is designed for participants living with chronic hepatitis B virus infection who are currently on standard nucleos(t)ide analogue (NA) therapy. Participants are grouped based on their Hepatitis B surface antigen (HBsAg) levels, with separate arms for those with high and low HBsAg levels.
  • What is the treatment process in this trial? The treatment process involves two main stages. In Stage 1, participants receive either DAP/TOM or a placebo. In Stage 2, eligible participants receive Bepirovirsen. Throughout these stages, participants continue their background NA treatment. After the Bepirovirsen treatment stage, there's an observation period where participants maintain their NA treatment. Finally, eligible participants discontinue their NA treatment.
  • What is considered a 'functional cure' in this study? In this study, a 'functional cure' for Hepatitis B virus (HBV) is defined as sustained suppression (24 weeks or longer) of HBV DNA below the lower limit of quantification after stopping all HBV treatments. Additionally, Hepatitis B surface antigen (HBsAg) should not be detected, with or without the presence of Hepatitis B Surface Antibody (HBsAb).
  • What are the main outcomes being measured in this trial? The primary outcome is the number of participants achieving a functional cure. Secondary outcomes include the number of participants achieving a functional cure with high or low baseline HBsAg levels, comparing results against a placebo group, and the number of participants with undetected HBsAg and HBV DNA below the lower limit of quantification at the end of Bepirovirsen treatment.

Ongoing Clinical Trials on Daplusiran

  • Study on the Effectiveness and Safety of JNJ-73763989 and Tenofovir Alafenamide in Patients with Hepatitis B and D Co-infection

    Not recruiting

    1 1
    Investigated drugs:
    France Italy Sweden

Glossary

  • Chronic Hepatitis B (CHB): A long-lasting liver infection caused by the hepatitis B virus that can lead to serious liver damage if left untreated.
  • Daplusiran/Tomligisiran (DAP/TOM): A combination of investigational drugs being studied for the treatment of chronic hepatitis B.
  • Bepirovirsen: An investigational drug being studied in combination with DAP/TOM for the treatment of chronic hepatitis B.
  • Nucleos(t)ide Analogue (NA) Therapy: A standard treatment for chronic hepatitis B that helps suppress the virus and slow down liver damage.
  • Hepatitis B surface antigen (HBsAg): A protein on the surface of the hepatitis B virus that can be detected in blood tests and indicates active infection.
  • Functional Cure: In this study, it refers to sustained suppression of HBV DNA and undetectable HBsAg after stopping all treatments.
  • HBV DNA: The genetic material of the hepatitis B virus that can be measured in blood to determine the level of viral activity.
  • Lower Limit of Quantification (LLOQ): The lowest amount of a substance that can be reliably measured by a specific laboratory test.
  • Hepatitis B Surface Antibody (HBsAb): An antibody produced by the immune system in response to the hepatitis B surface antigen, indicating immunity to the virus.

References

  1. https://clinicaltrials.gov/study/NCT06537414