About the study
The B-United study is testing an investigational therapy as a potential new treatment for chronic hepatitis B virus infection. If you are eligible and choose to participate, you will receive either a study drug called daplusiran/tomligisiran or placebo for the first 24 weeks, followed by a study drug called bepirovirsen for the next 24 weeks.* Placebos are used in clinical studies to help researchers evaluate study drugs by comparing the effects of a study drug to the effects of a placebo. You will be in the study for up to 110 weeks (approximately 26 months). It may be possible for some study visits to be performed at your home if your country and local regulations allow. Being in the study is your choice and voluntary. Although you may choose to leave the study at any time, it is important to know that your ongoing commitment to the B-United study is a key element in helping researchers find potential treatment options for people living with chronic hepatitis B virus infection around the world.
* There is a chance you may receive placebo for daplusiran/tomligisiran or may not be eligible to receive bepirovirsen. Eligibility for bepirovirsen will be based on blood tests and other assessments after the first 24 weeks of study treatment.
What are the study drugs?
Daplusiran/tomligisiran is designed to lower the level of a protein called hepatitis B surface antigen in your blood.
Bepirovirsen is designed to further lower the level of hepatitis B surface antigen in your blood and stop the virus from making it, which might allow the immune system to control the virus.
This investigational therapy is not currently approved for treating chronic hepatitis B virus infection. However, the study drugs have been given to adults in other clinical research studies. B-United is the first study in which the two study drugs are given in sequence to adults. What we learn in this study may help people living with chronic hepatitis B virus infection in the future.
What will happen during the study?
Informed Consent
Before you join this study, you need to fully understand what will happen. The study team will give you an informed consent form to read. This form describes the study in detail. The team will review this with you and answer any questions you may have. If you choose to join the study, you will sign the informed consent form.
Screening Stage (up to 8.5 weeks)
If you sign the informed consent form, you will proceed to the first stage of the study called Screening. In this stage, your eligibility to participate in the study will be assessed. Screening may be done at 1 or 2 study visits. The study doctor and team will:
- Review your medical history and ask you questions about your health
- Conduct medical procedures and tests, such as a physical examination, blood tests, and heart tests (electrocardiograms, also called ECGs)
- Review the results to find out if the study is right for you
Daplusiran/Tomligisiran or Placebo Stage (24 weeks)
If you are eligible and choose to participate, you will be placed in one of two groups (called study cohorts) depending on how much hepatitis B surface antigen you have in your blood.
- If you are in study cohort 1, you will receive daplusiran/tomligisiran every 4 weeks.
- If you are in study cohort 2, you will receive either daplusiran/tomligisiran or placebo every 4 weeks.**
- During this stage you will continue your NA treatment (whether you are in cohort 1 or 2). There are a total of 10 visits planned for this stage.
**If you are in study cohort 2, you will have a 5-in-6 chance of receiving daplusiran/tomligisiran and a 1-in-6 chance of receiving placebo. You will not know which you receive. The study doctor will also not know. This will be randomly assigned by a computer. The placebo has no active drug in it.
Bepirovirsen Stage (24 weeks)
When you complete study treatment with daplusiran/tomligisiran or placebo, your eligibility to receive bepirovirsen will be determined based on blood tests and other assessments. If eligible, you will:
- Receive bepirovirsen twice weekly for 2 weeks, then once weekly for the next 22 weeks
- Continue your NA treatment
- Have 26 study visits
If you are not eligible to receive bepirovirsen, you will not receive any study drug or placebo in this stage, but you will:
- Continue your NA treatment
- Have 8 study visits
On-NA Only Stage (24 weeks)
After you complete study treatment with bepirovirsen (or you are not eligible to receive bepirovirsen and you complete 8 visits), you will begin the On-NA Only stage. You will not receive any study drug or placebo in this stage. You will continue your NA treatment and have 9 study visits.
NA Cessation Stage or Continue on NA Stage (up to 28 weeks)
After the On-NA Only stage, you will either stop your NA treatment or continue NA treatment only. Eligibility to stop NA treatment will be based on blood tests and other assessments. If you stop your NA treatment, you will have 10 study visits. If you continue NA treatment only, you will have 2 visits.
Home Health Visits (where allowed)
As noted previously, it may be possible for some study visits to be performed at your home if your country and local regulations allow. You can ask the study doctor and staff if this may be an option for you. Home health visits are conducted by a qualified professional home nursing provider trained on the study. Assessments that may be performed as a home visit where allowed include giving study treatment injections, collecting blood samples, and collecting participant assessments.
What will happen at study visits?
You will receive study treatment injections at up to 32 visits. In addition, at all visits, the study doctor and team will conduct medical procedures and tests to check your hepatitis B virus infection and overall health. Study activities will vary from visit to visit and include:
Discussion with the study doctor and team†
Physical examination‡
Measurement of vital signs (body temperature, pulse rate, respiratory rate, and blood pressure)
Blood tests
Urine tests
Pregnancy test (if applicable)
Some visits may also include activities not shown here. The study doctor and team will review the visit schedules with you and explain all activities.
†Discussion may include review of changes in your health, side effects, medications you take, and contraception (if applicable).
‡The physical examination may not be needed if you are not experiencing any new symptoms.
What will be expected of me during the study?
Studies like this one rely on the cooperation of volunteer participants. While you are in this study, you will be expected to:
- Understand the commitment to participating in this study, as explained by the study doctor and team
- Follow instructions from the study doctor and team
- Come to your study visits and complete all scheduled activities
- Report any changes in your health, even if you don’t think the changes are important or related to the study
- Keep your contact information current with the study team
- Talk with the study doctor before you begin taking any new medications or supplements during this study
- Tell the study doctor or team if you no longer want to be in the study
- Follow all requirements related to lifestyle, including contraception, as explained by the study doctor and team
You will have the full support of the study doctor and team. They will answer any questions you may have about what is expected of you.
Lifestyle requirements:
- We ask that you do not drink alcohol 24 hours before your visits;
- Please note that tobacco products and nicotine-containing products are not likely to be allowed in the clinical unit or hospital;
- We ask that you avoid heavy exercise for 48 hours before your visits and avoid changing your regular exercise regime/intensity during the study;
- We ask that you do not take creatine-containing pills (which some people use as a gym supplement) during the study.
Who Can Participate
You may be eligible to participate if you:
- Are at least 18 years old (the minimum age may be higher in some countries)
- Have had diagnosed chronic hepatitis B virus infection for at least 6 months
- Have been on stable nucleoside / nucleotide analogue (NA) treatment (sometimes referred to as antivirals, such as tenofovir or entecavir) for the past 6 months, without any changes for the past 3 months
You will also need to meet additional requirements. The study doctor will review these with you.
About clinical studies
Clinical studies, also called clinical trials, are done to test investigational medications for diseases and conditions. Studies help determine if investigational medications are safe to use and work to improve the health of people. Before any medication can be approved and made available to the general public, it has to go through several phases of clinical research.
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Why do people participate in clinical studies?
People participate in studies for a variety of reasons. Some volunteers may participate because they want to learn more about their disease or health condition. Others volunteer to participate because they want to help researchers learn more about a disease or health condition. What researchers learn may help future patients.
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Are clinical studies safe?
Studies follow a specific set of standards and are closely regulated to help protect the safety of all participants. Each study also includes strict safety measures to protect participants. In addition, each study follows a written plan called a protocol. The protocol is designed to make sure all study procedures are conducted correctly and safely.
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What if I have questions during the study?
You can ask questions at any point before, during, and after the study. Before agreeing to participate, please make sure you understand the responsibilities of being a study participant. If you have any concerns about the study, you should discuss them with the study team at any time.
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What if I want to stop participating in the study?
Participation is completely voluntary, and you can end your participation at any time, for any reason. If you think you would like to stop participating in the study, talk to the study doctor and team. There will be no negative impact on the usual care you receive outside the study.
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Can I see other doctors during the study?
You can visit any healthcare provider to meet your needs during the study. Please let the study team know if you will be seeing another healthcare provider and if any medication is prescribed.
Resources
The following websites include additional information you might find helpful.
https://www.cdc.gov/hepatitis/hbv/
https://www.who.int/en/news-room/fact-sheets/detail/hepatitis-b
Locations
Click on the map below to find a study site located near you.