A study to assess the effectiveness and safety of RO7790121 for induction therapy in participants with moderately to severely active ulcerative colitis

1. Why is this study needed?

Ulcerative colitis (UC) is a health issue that causes inflammation in the inside layer of some parts of the bowel. It often affects the rectum and the lower colon – also called the large intestine. It can cause bleeding sores or mucus to form. This leads to frequent loose stools or bowel movements and bleeding from the rectum. When UC is ‘moderate to severe’, a person will have 6 to 10 urgent bowel movements per day that are sometimes bloody. When UC is ‘severe’, a person will have more than 10 urgent bloody bowel movements per day. When people with UC have symptoms, their UC is said to be ‘active’. People with moderately and severely active UC might also have pain in the belly, tiredness and weight loss.

Standard treatments for UC include medicines that reduce inflammation, such as corticosteroids, biologics and small molecules. But for many people living with UC, symptoms do not improve even with these treatments. Treatment can also stop working after a time or cause unacceptable unwanted effects that affect a person’s ability to continue on a therapy and function. So, better treatments for UC are needed.

This study is testing a medicine called RO7790121. RO7790121 is an investigational medicine being developed to treat UC. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not yet approved RO7790121 for treating UC.

This study aims to compare RO7790121 with a ‘placebo’. A placebo is a medicine that contains no active ingredients but looks the same as the study medicine. Researchers want to see if RO7790121 works, how well it works and how safe it is. This is compared to a placebo in people living with moderately to severely active UC.

2. Who can take part in the study?

People aged 18 to 80 years old, and 16 to 17 years old in some countries, with moderately to severely active UC can take part in the study. Their UC diagnosis must have been confirmed by an ‘endoscopy’. An endoscopy is a procedure where a doctor uses a flexible tube with a camera on it to look inside the large intestine (colon). To take part, people also must have taken at least 1 other medicine for UC that didn’t work very well, stopped working or caused unacceptable unwanted effects.

People cannot take part in this study if they have severe UC that requires a hospital stay for treatment, such as surgery. People who have certain other medical conditions, such as Crohn’s disease, abnormal cells in their bowel (known as ‘dysplasia’), some types of cancer within the last 5 years, or certain infections also cannot take part. People who are trying to get pregnant, plan to get pregnant or currently breastfeeding cannot take part in the study.

3. How does this study work?

This study consists of a screening period, a treatment period of 12 weeks, an optional treatment extension period and a safety follow up period of 12 weeks. Participants will be screened to check if they are able to participate in the study. The screening period will take place from 1 day to 35 days before the start of treatment. 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. Comparing results from the different groups helps researchers know if any changes seen result from the study medicine or occur by chance.

Everyone who joins this study will be placed into 1 of 2 groups randomly. Participants will be given either RO7790121 OR a placebo, given as a drip into a vein (known as an infusion) for four times. Participants will have a 3 in 5 chance of being placed in the RO7790121 group and a 2 in 5 chance of being placed in the placebo group.

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.

If participants agree and the study doctor thinks it's suitable, they can keep receiving treatment in an extension of the study, after completing the 12-week treatment period. Everyone who joins the extension will be given RO7790121. This is given as an injection under the skin every 2 or 4 weeks. The extension is open-label. This means everyone involved, including the participant and the study doctor, will know the participant has been given RO7790121.

During this study, the study doctor will see participants regularly. Some visits may take place in the participant’s home by a nurse if they prefer. The study doctor will see how well the treatment is working and any unwanted effects participants may have. Participants will have 2 follow-up visits after 6 weeks and 3 months of completing the study treatment, during which the study doctor will check on the participant’s wellbeing. Total time of participation in the study could be more than 7 months if they take part in the extension of the study. 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 result measured in the study to assess if the medicine has worked is the number of participants who have no or very few signs of UC at 3 months.

Other key results measured in the study include:

• The average number of bowel movements per day and amount of bleeding from the rectum after 2 weeks of treatment compared to the start of the study
• The number of participants who have fewer or no bleeding sores, less or no mucus, and reduced signs of inflammation, in the large intestine at 3 months. This is assessed with an endoscopy
• The number of participants who have at least a 30% reduction in signs of UC (number of bowel movements per day, amount of bleeding and endoscopy results) at 3 months
• How much participants report their UC symptoms have changed and how severe symptoms are
• The number and seriousness of unwanted effects

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.

RO7790121
RO7790121 has had limited testing in humans. The potential unwanted effects of this medicine are based on human and laboratory studies, or knowledge of similar medicines. These include allergic reactions, feeling sick and joint pain. There might be other unwanted effects that are not known at this time.

Known unwanted effects of infusions include pain, bruising, redness, warmth, burning, stinging or itching on the skin where it has been pricked with a needle to give a treatment. Other unwanted effects of infusions can include throwing up, wanting to throw up, a feeling of coldness that makes the body shiver, low or high blood pressure, fever, pain or discomfort in the head.

Known unwanted effects of injections under the skin include a reaction, swelling or rash on the skin where it has been pricked with a needle to give a treatment.

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