About the Study

B-Well is a phase 3 clinical research study testing a drug, called bepirovirsen, as a potential new treatment for chronic hepatitis B virus infection. If you are eligible and choose to participate, you will receive either bepirovirsen or placebo twice a week for 2 weeks, then once a week for 22 more weeks. The placebo has no active drug. 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 80 or 104 weeks (18.5 or 24 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 your participation is completely voluntary and you may choose to leave the study at any time, it is important to know that your ongoing commitment to the B-Well study is a key element in helping researchers find potential treatment options for people living with chronic hepatitis B virus infection around the world.

What is the study drug?

Bepirovirsen (the study drug) is designed to stop the virus from making substances that we think may prevent the immune system from fighting the virus. By stopping the virus from making those substances, bepirovirsen may potentially allow the body to gain control over the infection.

Bepirovirsen is not currently approved for use in treating chronic hepatitis B virus infection in the general public. However, it has been given to adults in other clinical studies.

What will happen during the study?

Screening (up to 8.5 weeks)

The first stage of the study is called Screening. In this stage, your eligibility to participate in the study will be assessed in two parts.

First, you will learn about the study and ask the study doctor and staff questions to be sure you understand what the study involves. After your questions have been answered, if you want to participate in the study, you will sign the informed consent form. The study doctor and staff will conduct some initial blood tests to learn more about your hepatitis B. If the results show that you may be eligible, you will continue with the second part of the Screening stage.

The second part of the Screening stage will include a physical examination, questions about your medical history, and additional medical tests. This will include more blood tests, urine testing, a test to check your heart called an electrocardiogram (ECG), and other assessments. The study doctor will review the results of all Screening tests and assessments to determine if you are eligible to participate in the study.

Study Treatment (24 weeks)

If you are eligible and choose to participate, a computer will randomly assign you to one of two study groups. One group will receive the study drug (bepirovirsen); the other will receive placebo. The placebo has no active drug in it.

You will have a 2 in 3 chance of being in the study drug group and a 1 in 3 chance of being in the placebo group. You will not know which group you are in. The study doctor will also not know.

You will be given the study drug or placebo as two injections under the skin twice a week for the first 2 weeks, then once a week for 22 more weeks during the Study Treatment visits. You will also continue your nucleoside/nucleotide analogue (NA) treatment (sometimes referred to as antivirals, such as tenofovir or entecavir).

On-NA Only (24 weeks)

After 24 weeks, you will begin the next stage. You will not receive the study drug or placebo during this stage, but you will continue your NA treatment. You will have 9 study visits in 24 weeks. Most study visits in this stage will be 2 or 4 weeks apart. At the last visit, the study doctor will determine if you are eligible to stop NA treatment based on blood tests and other assessments.

Follow-up (24 or 48 weeks)

During the Follow-up stage, you will either stop your NA treatment or continue NA treatment only, depending on test results from the last visit in the previous stage.

If you stop NA treatment, you will have 15 study visits in 48 weeks. The first 6 visits will be 2 weeks apart; the remaining visits will be every 4 weeks.

If you continue NA treatment during this stage, you will have 2 study visits in 24 weeks, with 12 weeks between 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. 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?

The study doctor will conduct tests and examinations at study visits to check your hepatitis B virus infection and overall health. Study activities will vary from visit to visit and include:

• Discussions about your health and medications you may take outside the study
• Measurement of vital signs (oral temperature, pulse rate, respiratory rate, and blood pressure)
• Collection of blood and urine samples
• Physical examination
• Questionnaires about your health and well-being
• Review of any side effects that you may be experiencing

Study visits may also include activities not listed here. The study doctor will review the schedule with you and explain the study visit activities.

What will be expected of me during the study?

As a study participant, you will have the full support of the study doctor and staff. While you are in this study, you will need to:

• Follow instructions from the study doctor and staff
• Come to your study visits and complete all scheduled activities
• Have study treatment (study drug or placebo) as assigned and scheduled
• 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 staff
• Understand the commitment to participating in this study, as explained by the study doctor and staff
• Talk with the study doctor before you begin taking any new medications or supplements during this study
• Tell the study doctor or staff if you no longer want to be in the study
• Follow all requirements related to lifestyle issues, including contraception, as explained by the study doctor and staff