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Tomligisiran

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.

Table of Contents

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[1]. 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[1].

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[1]. 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[1].

Treatment Arms

The clinical trial is divided into several treatment arms, each testing different combinations and doses of the drugs[1]:

  1. 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
  2. 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[1].

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[1]:

  • 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[1].

Potential Benefits

If successful, TOMLIGISIRAN in combination with bepirovirsen could offer several potential benefits for patients with chronic hepatitis B[1]:

  • 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[1].

Aspect Details
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

FAQ

  • What is the main goal of this clinical trial? The main goal 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 therapy.
  • What is meant by 'functional cure' in this study? A functional cure for hepatitis B virus (HBV) is defined as sustained suppression of HBV DNA below detectable levels for 24 weeks or longer after stopping all HBV treatments, with hepatitis B surface antigen (HBsAg) not detected, with or without hepatitis B surface antibody (HBsAb) present.
  • How is the study designed? The study is a phase 2b, multi-center, randomized, partially placebo-controlled, double-blind trial. Participants are divided into groups based on their hepatitis B surface antigen (HBsAg) levels and receive different doses of DAP/TOM or placebo, followed by Bepirovirsen treatment.
  • What happens after the treatment stages in this trial? After the treatment stages, participants enter an observation period called the NA Only Stage, where they continue their background nucleos(t)ide analogue treatment. Eligible participants may then discontinue this background treatment.
  • How will the effectiveness of the treatment be measured? The effectiveness will be primarily measured by the number of participants achieving a functional cure. Secondary outcomes include measuring functional cure rates in participants with high and low baseline HBsAg levels, and comparing results against a placebo group.

Ongoing Clinical Trials on Tomligisiran

  • 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.
  • Tomligisiran: An experimental drug being studied as part of a combination therapy for treating chronic hepatitis B.
  • Daplusiran: Another experimental drug used in combination with Tomligisiran in this study for treating chronic hepatitis B.
  • Bepirovirsen: A medication used in the second stage of treatment in this clinical trial for 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.
  • 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.
  • HBV DNA: The genetic material of the hepatitis B virus that can be measured in blood to determine the level of viral activity.
  • Functional cure: In hepatitis B, it refers to sustained suppression of the virus without detectable surface antigen after stopping all treatments.
  • Lower limit of quantification (LLOQ): The lowest amount of a substance that can be reliably measured by a specific laboratory test.

References

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