A study to compare two different formulations of ocrelizumab given under the skin in participants with multiple sclerosis

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 defence, which protects the body from foreign or harmful substances such as bacteria and viruses. There are limitations to the available treatments for MS. Sometimes they are not convenient, depending on how often they need to be taken, or the unwanted effects they cause. Some treatments can also take several hours to be given, such as an infusion. More options for how treatment is given are needed.

This study is testing a new formulation of a medicine called ocrelizumab for injection under the skin, which is called a subcutaneous (SC) injection. It is being developed to treat MS.

The new formulation of ocrelizumab is an experimental medicine. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not approved the new formulation of ocrelizumab for the treatment of multiple sclerosis. The original formulation of ocrelizumab for injection under the skin has been approved by multiple health authorities, including in the United States and Europe.

The purpose of this study is to see how the body responds to two different ocrelizumab formulations for SC injection. We want to compare the new formulation and the original formulation to see:

• If the same amount of drug is taken up by the body
• If it is safe and well tolerated
• How the drug affects the body
• How the immune system reacts to the drug.

2. Who can take part in the study?

People of 18 - 65 years of age with a diagnosis of relapsing MS (RMS) or primary progressive MS (PPMS) can take part in the study.

RMS is known for periods where new or existing symptoms get worse (relapse) followed by a period of recovery (remission). During remission, few symptoms are present. PPMS is where symptoms and disability gradually get worse. There are no periods of relapse or remission.

People may not be able to take part in this study if they have had treatment previously with certain MS medications.

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 up to 6 weeks before the start of treatment.

Everyone who joins this study will be put into one of two groups randomly (like flipping a coin) for their first treatment at the start of the study. They will be given either the new formulation of ocrelizumab or the original formulation of ocrelizumab. Both formulations will be given as an SC injection. Participants will have an equal chance of being placed in either group.

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.

After the first treatment, everyone will be given six more treatments with the new formulation of ocrelizumab. These will be given as an SC injection once every 6 months.

The total time of participation in the study will be about 3.5 years. During this study, the study doctor will see participants about 27 times. There are 10 visits in the first month after the first SC injection, and then the visits become less frequent. They will check for any unwanted effects participants may have. Participants will have one follow-up visit 6 months after completing the study treatment, during which the study doctor will check on the participant’s well being. 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 to compare the two formulations of ocrelizumab are the levels of ocrelizumab in the blood. This will be assessed from when the first injection is given until the participant finishes the study. Other key results measured in the study include the number and type of unwanted effects and the results of other safety assessments.

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 drugs
Participants may have unwanted effects of the drugs 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 for injection under the skin
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: injection reaction (including redness, itching, swelling, headache), respiratory infections (including cold, sinus infection, inflamed tonsils, sore throat, or flu). It could make it harder for the immune system of participants to fight a new infection. 

The study medicine(s) may be harmful to an unborn baby. Women must take precautions to avoid exposing an unborn baby to the study treatment.