A study to assess the efficacy and safety of RO7790121 in patients with moderate to severe rheumatoid arthritis who have not responded to or who cannot tolerate TNF and/or JAK inhibitors

1. Why is this study needed?

Rheumatoid arthritis (RA) is an autoimmune and inflammatory condition, which means that the immune system attacks healthy cells in the body by mistake. It causes painful swelling in the affected parts of the body. RA mainly attacks the joints, usually many joints at once. There are several medicines that can help treat RA. Some are called TNF inhibitors which block a protein that causes inflammation. Others are called  JAK inhibitors, which stop certain signals in the body that lead to  inflammation. But not everyone gets better with these treatments, and some people cannot tolerate them. So new treatment options are needed that can help more people and keep the disease under control for a  longer time.

This study is testing a medicine called RO7790121. It is being developed to treat moderate to severe RA.

RO7790121 is an experimental medicine. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not approved RO7790121 for the treatment of RA.

This study aims to compare the effects of RO7790121 against non-active medicine (placebo) and to check how safe it is in people with moderate to severe RA.

2. Who can take part in the study?

People (males and females) of 18 years or older with moderate to severe RA can take part in the study. They can also join the study if previous treatments like TNF or JAK inhibitors did not work for them or if they cannot take these treatments.

People may not be able to take part in this study if two or more treatments (such as TNF or JAK inhibitors) did not work for them. They may also be excluded if they have other joint diseases, certain infections, or other conditions that weaken the immune system.

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 from 28 days before the start of treatment.

Everyone who joins this study will be placed into groups randomly (like flipping a coin) and given either RO7790121 or placebo, as an injection under the skin (subcutaneous injection). At first, injections will be more often, then less so as the study goes on. The group receiving placebo will start getting RO7790121 half way through the study. Participants will have a higher chance of being placed in the study drug RO7790121 group than in the placebo group.

This is a ‘placebo-controlled’ study. This means that participants are put in a group that will receive a medicine or a group that will receive ‘placebo’ (a medicine that contains no active ingredients but looks the same and is taken in the same way as the study medicine). Comparing results from the different groups helps researchers know if any changes seen result from the study medicine or occur by chance.

This is a double-blinded study. This means that neither the participants in the study nor the team running it will know which treatment is being given until the study is over. This is done to make sure that the results of the treatment are not affected by what people expected from the received treatment. However, the study doctor can find out which group the participant is in, if the participants' safety is at risk.

During this study, the study doctor will see participants regularly. They will see how well the treatment is working and any unwanted effects participants may have. Participants will have a follow-up visit after completing the study treatment.  Depending on this visit, they might be able  to keep taking RO7790121 in a long term (extension) study. If they  do not join the longer study, they will still have a safety follow-up visit sometime after completing the study treatment. The study doctor will check on the participant’s well being. Total time of participation in the study will be less than a year. 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 assess if the medicine has worked are the changes in the DAS28 CRP score. This score helps to see how active the RA disease is. This  score is based on how many joints are swollen or painful, how  the study doctors and participants rate the severity of arthritis and the level of C-Reactive protein (a substance in blood that shows  inflammation).

Other key results measured in the study include

• How many participants have a 20%, 50%, and 70% improvement in RA symptoms during the study
• Number and seriousness of unwanted effects
• How RO7790121 gets to different parts of the body, and how the body changes and gets rid of it

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 medicine
Participants may have unwanted effects of the medicine 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.

RO7790121
RO7790121 has had limited testing in people and has not been tested in people with RA. Therefore, the unwanted effects of this medicine are not known now. Participants will be told about the possible unwanted effects based on laboratory studies or knowledge of similar medicines. This includes a reaction on the skin where it has been pricked with a needle to give a treatment. Symptoms of this may include dark purple marks (bruising), warmth, burning, stinging, redness, pain, itching, or swelling around the site of injection. There is also a risk of a very serious allergic reaction that can cause breathing to stop (anaphylaxis).

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.