A study to look at how well ocrelizumab works when given as an injection under the skin in people with multiple sclerosis who switch from an approved treatment called anti-CD20 therapy

1. Why is this study needed?

Multiple sclerosis (MS) is a health condition in which the immune system attacks the protective covering of nerve fibres in the brain and spinal cord. This leads to communication problems between the brain and the rest of the body. The immune system is the body's natural defense, which protects the body from foreign or harmful substances such as bacteria and viruses. There are different types of MS. In relapsing multiple sclerosis (RMS), the signs or symptoms of MS return after they have improved for a while. This return of symptoms is called a relapse. In primary progressive multiple sclerosis (PPMS), the symptoms worsen over time. MS can change from person to person, and while there is no cure, treatments can help manage symptoms and slow the disease's progression.

Anti-CD20 therapy is a type of treatment that is used in MS. It destroys certain types of white blood cells (called B cells) that are thought to play a role in MS.

In this study the participants will switch from their current anti-CD20 therapy and receive a medicine called ocrelizumab given as an injection under the skin. It is approved for treating RMS and PPMS.

This study aims to look at the effects of ocrelizumab on damaged areas in the brain called brain lesions. This study will also look at the overall participants’ experience, good and bad effects, and safety in people with RMS or PPMS. This study will test the satisfaction of participants and doctors with this treatment and also with the previous treatment.

2. Who can take part in the study?

People, both males and females, aged 18 to 65 years with RMS or PPMS can take part in the study. Participants must be able to sign the informed consent form and follow the study instructions. This consent form means that participants are agreeing to take part after reviewing the study details. Participants must meet specific health and treatment history requirements (switching from an approved anti-CD20 therapy). Additionally, participants must have the required disability score at screening or within 6 months of screening. Screening means to see if participants can take part in the study.

People may not be able to take part in this study if they have certain health conditions, used certain previous treatments, or have other factors that could affect their safety or the study results. This includes taking certain medications, having a history of cancer, or certain brain conditions. This also includes liver conditions, certain infections, or participating in another study. People who are pregnant, or currently breastfeeding cannot take part in the study.

3. How does this study work?

People will be screened to check if they are able to participate in the study. The screening period will take place up to 28 days before the start of treatment in this study.

Everyone who joins this study will be given a treatment called ocrelizumab as an injection under the skin. This treatment will be given at the beginning of the study and then again in about 6 months.

This is an open-label study. This means everyone involved, including the participant and the study doctor, will know the study treatment the participant has been given.

During this study, the study doctor will see participants within 4 weeks of the screening visit. This is the first treatment visit. The second treatment visit will happen about 24 weeks after the first treatment. Participants will have a total of 2 treatment visits. The study doctor will give participants ocrelizumab as an injection under the skin. The study doctor will look at overall health, any unwanted effects, and how satisfied participants are with the treatment. The study doctor may also do some tests to look for specific markers in the blood that can help understand how the treatment is working and its effects on their MS. Participants will have one follow-up visit about 24 weeks after receiving their second treatment. During this last visit, the study doctor will check on the participant's well-being and monitor their health. Total time of participation in the study will be about 12 months. Participants have the right to stop study treatment and leave the study at any time, if they wish to do so.

4. What are the main results measured in this study?

The main results measured in the study include evaluating whether switching to the study medication affects certain brain changes seen on magnetic resonance imaging scans (MRI scans). An MRI scan is a detailed picture of the inside of the body, like the brain, taken with a special machine. The researchers will use the MRI to check if there are changes in the number or size of certain types of brain lesions. Participants will have an MRI before the first treatment to help determine if there are changes at 24 and 48 weeks after treatment. There are a total of 3 MRIs in the study.

Other key results measured in the study include

• Checking if there are no new or changes in the size of old brain lesions at 24 weeks
• Monitoring the safety of the treatment by tracking any unwanted effects during the study
• Evaluating whether switching to the new treatment affects certain brain changes seen on MRI scans at 48 weeks

At 24 and 48 weeks the researchers will check how the treatment affects immune cells. Immune cells are a group of cells in the body that help protect a person from germs and keep a person healthy. The researchers will also ask participants about their satisfaction with their previous treatment and the new treatment at different points during the study.

5. Are there any risks or benefits in taking part in this study?

Taking part in the study may or may not make participants feel better. But the information collected in the study can help other people with similar health conditions in the future.

It may not be fully known at the time of the study how safe and how well the study treatment works. The study involves some risks to the participant. But these risks are generally not greater than those related to routine medical care or the natural progression of the health condition. People interested in taking part will be informed about the risks and benefits, as well as any additional procedures or tests they may need to undergo. All details of the study will be described in an informed consent document. This includes information about possible effects and other options of treatment.

Risks associated with the study drug
Participants may have unwanted effects of the drug used in this study. These unwanted effects can be mild to severe, even life-threatening, and vary from person to person. During this study, participants will have regular check-ups to see if there are any unwanted effects.

Ocrelizumab
Participants will be told about the known unwanted effects of ocrelizumab, and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines. Known unwanted effects include redness, pain, swelling, bruising, itching, headache, flu, common cold, sore throat, and a decrease in specific proteins in the blood which help protect against infection.

The study medicine may be harmful to an unborn baby. Women and men must take precautions to avoid exposing an unborn baby to the study treatment.