Study of GSK3965193 and Bepirovirsen for People Living with Chronic Hepatitis B Infection and Healthy Participants

What is this study about?

This study involves people with Hepatitis B, which is a long-term infection of the liver caused by the hepatitis B virus. The study will test a medication called GSK3965193 given as tablets by mouth, both alone and in combination with another medication called bepirovirsen given as an injection under the skin. Some participants will receive placebo instead of the actual medications. All participants in the study will continue taking their regular hepatitis B medications during the study.

The purpose of this study is to check the safety and effects of GSK3965193 when used alone and when combined with bepirovirsen in people living with chronic hepatitis B infection. The study will look at how well these medications are tolerated, how they work in the body, and whether they can reduce the amount of hepatitis B virus and virus-related proteins in the blood. The study is divided into four parts, with some parts testing the medication alone and other parts testing the combination of both medications.

During the study, participants will receive treatment for several weeks and will be monitored both during treatment and after treatment ends. The study will measure various markers of hepatitis B infection in the blood, including the amount of virus and specific proteins produced by the virus. Safety will be checked through regular blood tests, physical examinations, and monitoring for any unwanted effects. The total length of follow-up will vary depending on which part of the study participants join, with some participants being followed for several months after treatment to see the longer-term effects of the medications.

1 Screening and eligibility confirmation

Your eligibility for the trial will be assessed based on specific criteria. This includes confirmation that you have had chronic hepatitis B infection for at least 6 months.

You must be currently taking stable medication to control the virus, such as tenofovir or entecavir. This medication must have been unchanged for at least 6 months before entering the trial, and no changes are planned during the trial.

Blood tests will be performed to measure specific markers. Your HBsAg level (a protein on the surface of the hepatitis B virus) must be greater than 100 IU/mL. Your HBV DNA level (the genetic material of the virus) must be less than 90 IU/mL.

Your ALT level (a liver enzyme that indicates liver health) must be no more than 2 times the upper limit of normal.

A pregnancy test will be performed if applicable, and contraception requirements will be explained.

2 Baseline assessment

Before treatment begins, baseline measurements will be taken. This includes blood tests to measure HBsAg levels, liver function tests, and other laboratory parameters.

Vital signs such as blood pressure and heart rate will be recorded.

An electrocardiogram (a test that measures the electrical activity of your heart) will be performed.

Sensory nerve conduction tests may be conducted to assess nerve function.

3 Treatment period with GSK3965193

You will receive either GSK3965193 or a placebo (an inactive substance that looks like the real medication). The placebo is used for comparison purposes. You will not know which one you are receiving, as this is a double-blind study.

GSK3965193 is taken orally in tablet form. The specific dosage, frequency, and duration will be determined by the study protocol for your assigned group.

The treatment period with GSK3965193 or placebo lasts for 4 weeks.

You will continue taking your regular hepatitis B medication during this time.

Regular monitoring will occur during this period, including blood tests to measure HBsAg levels and other safety parameters.

4 Post-treatment follow-up after GSK3965193

After completing the 4-week treatment period, you will be monitored for an additional 2 weeks.

Blood tests will continue to measure HBsAg levels and assess how your body responds after stopping the study medication.

Safety assessments will continue, including laboratory tests and monitoring for any side effects.

5 Optional extension with bepirovirsen (if applicable)

Depending on your assigned group and response, you may be offered the option to continue with bepirovirsen treatment.

Bepirovirsen is administered as an injection under the skin (subcutaneous injection).

The specific dosage, frequency, and duration of bepirovirsen treatment will be determined by the study protocol.

This extension phase is optional and will only proceed if you agree to continue.

6 Combination treatment (for selected participants)

Some participants will receive a combination of GSK3965193 and bepirovirsen together.

GSK3965193 will be taken orally as tablets, while bepirovirsen will be given as injections under the skin.

The duration and specific schedule of this combination treatment will be determined by the study protocol.

You will continue taking your regular hepatitis B medication throughout this period.

Regular monitoring will include blood tests to measure HBsAg levels, HBV DNA levels, and safety parameters.

7 Extended follow-up period

After completing treatment with bepirovirsen, you will be monitored for an extended period of at least 6 months.

The purpose of this follow-up is to assess whether the treatment has achieved a complete response, defined as undetectable levels of both HBV DNA and HBsAg for 6 consecutive months.

Blood tests will be performed regularly to measure these viral markers.

Safety assessments will continue throughout this period to monitor for any delayed side effects.

8 Contraception requirements during and after treatment

If you are male, you must refrain from donating sperm during treatment and for at least 7 days after the last dose of GSK3965193 alone, or 90 days after the last dose of bepirovirsen if you receive combination treatment.

If you are male and sexually active with a woman who can become pregnant, you must use a condom during this time.

If you are female and able to become pregnant, you must use highly effective contraception during treatment and for at least 7 days after the last dose of GSK3965193 alone, or 90 days after the last dose of bepirovirsen.

Pregnancy tests will be performed at specified times during and after the study to ensure you are not pregnant.

9 Safety monitoring throughout the trial

Throughout the entire trial, your safety will be closely monitored. This includes regular blood tests to check liver function, blood cell counts, and kidney function.

Vital signs such as blood pressure, heart rate, and temperature will be measured at each visit.

Electrocardiograms will be performed periodically to monitor heart function.

Sensory nerve conduction tests may be repeated to assess nerve function.

Any side effects or adverse events will be recorded and assessed by the medical team.

You should report any new symptoms or health changes to the study team promptly.

Who Can Join the Study?

You must be between 18 years old (or the legal age to give consent in your area) and 65 years old when you sign the consent form
Your body weight must be at least 50 kilograms (about 110 pounds) and your body mass index (a measure of body fat based on height and weight) must be between 18 and 32
If you are a male participant, you must agree to not donate sperm during the study and for at least 7 days after your last dose in some parts of the study, or 90 days in other parts. You must also either avoid sexual intercourse with women or use a condom during sex with women who could become pregnant
If you are a female participant, you must not be pregnant or breastfeeding. You must either be unable to become pregnant, or if you can become pregnant, you must use a highly effective birth control method (one that works more than 99% of the time) during the study and for at least 7 days after your last dose in some parts, or 90 days in other parts
If you are a woman who can become pregnant, you must have a negative pregnancy test before starting the study
You must have had chronic hepatitis B infection (a long-term liver infection caused by the hepatitis B virus) for at least 6 months before joining the study, confirmed by medical records
You must currently be taking stable nucleos(t)ide analog therapy (a type of antiviral medication such as tenofovir or entecavir). Stable means you have been taking the same medication without changes for at least 6 months before joining the study
Your blood level of HBsAg (hepatitis B surface antigen, a protein from the virus found in the blood) must be greater than 100 international units per milliliter
Your blood level of HBV DNA (the genetic material of the hepatitis B virus) must be less than 90 international units per milliliter
Your ALT (alanine aminotransferase, a liver enzyme measured in blood tests to check liver health) must be no more than 2 times the upper limit of normal

Who Cannot Join the Study?

Pregnant women or women who are breastfeeding cannot participate in this study, as the medications being tested may harm an unborn baby or nursing infant.
People with severe liver damage (also called decompensated cirrhosis), which means the liver is not working properly and has serious complications like fluid buildup in the abdomen, bleeding problems, or confusion.
Patients who have liver cancer or signs that suggest liver cancer may be present.
People with HIV infection (a virus that weakens the immune system) or Hepatitis C infection (another type of liver virus).
Patients who have received antiviral medications for Hepatitis B within a certain time period before joining the study, as this may affect the study results.
People who have had an organ transplant, as they require special medications that may interfere with the study treatment.
Patients with serious heart, kidney, or lung diseases that are not well controlled.
People who have cancer or have had cancer treatment within a recent time period.
Patients with uncontrolled medical conditions or diseases that could make it unsafe to participate in the study.
People who are taking certain medications that interact with the study drugs and cannot be stopped safely.
Patients with abnormal laboratory test results that show the kidneys, liver, or blood cells are not functioning within safe limits for the study.
People who have had a severe allergic reaction to similar medications in the past.
Patients who are unable to follow the study requirements or attend regular clinic visits.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
CHU Grenoble Alpes	La Tronche	France

Other Sites

Site Name	City	Country
Fondazione IRCCS San Gerardo Dei Tintori	Monza	Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milan	Italy
Centre Hospitalier Universitaire De Nantes	Nantes	France
Centre Hospitalier Universitaire De Rennes	Rennes	France
Czd Cwknp Rlqbjoaiedr	Lyon	France

Trial status

Country	Status	Recruitment Start
France	Not recruiting	23.09.2024
Italy	Not recruiting	23.09.2024

Trial locations

Investigated drugs:

Bepirovirsen

GSK3965193 is an investigational medication being tested as a treatment for chronic hepatitis B infection. In this study, it is given by mouth and is being evaluated both on its own and in combination with another medication to see how well it works and how safe it is for people living with chronic hepatitis B.

Bepirovirsen is a medication being tested for the treatment of chronic hepatitis B infection. In this study, it is being used in combination with GSK3965193 to evaluate how well the two medications work together and to assess their safety in people living with chronic hepatitis B.

Investigated diseases:

Chronic hepatitis B

Hepatitis B – Hepatitis B is a viral infection that affects the liver and is caused by the hepatitis B virus. The virus spreads through contact with infected blood or other body fluids. When a person becomes infected, the virus can cause both acute and chronic forms of the disease. In the acute phase, some people may experience symptoms while others have no symptoms at all. Chronic hepatitis B develops when the virus remains in the body for more than six months and continues to damage the liver over time. The chronic form can lead to progressive liver damage and scarring of the liver tissue.

Trial ID:

2023-509684-24-00

Protocol code:

214760

NCT ID:

NCT05330455

Trial Phase:

Phase I and Phase II (Integrated) – First administration to humans

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Study of GSK3965193 and Bepirovirsen for People Living with Chronic Hepatitis B Infection and Healthy Participants

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?